Breast Cancer Tissues (breast + cancer_tissue)

Distribution by Scientific Domains


Selected Abstracts


Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2006
Eriko Tokunaga
Abstract Akt/PKB is a serine/threonine kinase that plays an important role in survival when cells are exposed to different apoptotic stimuli. Aberrant activation of Akt/PKB in breast carcinoma is associated with poor prognosis and resistance to endocrine therapy and chemotherapy. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Breast cancer tissues obtained from 252 patients were utilized for this study. We evaluated Akt activation by immunohistochemical assessment of the expression of phosphorylated Akt (pAkt) at Ser-473. Eighty-four cases (33.3%) were diagnosed as positive for pAkt expression. pAkt was significantly associated with HER2/neu overexpression (p < 0.0001). There was an inverse correlation between pAkt and PR expression (p = 0.0321); however, there was no association between pAkt and ER expression. Survival analysis showed that pAkt positivity was associated with poor disease-free survival in cases with postoperative hormone therapy; however, there was no association in cases without hormone therapy. Our results indicate that Akt activation induced poor prognosis in patients who received adjuvant hormone therapy. This finding suggests that inhibition of the Akt signaling pathway may increase the efficacy of hormone therapy and improve the prognosis of patients who receive adjuvant hormone therapy. © 2005 Wiley-Liss, Inc. [source]


Raman spectroscopic analysis of breast cancer tissues: identifying differences between normal, invasive ductal carcinoma and ductal carcinoma in situ of the breast tissue

JOURNAL OF RAMAN SPECTROSCOPY, Issue 10 2007
Shazza Rehman
Abstract A relatively non-destructive method employing Raman spectroscopy for the analysis of histopathological specimens is described. Raman spectroscopy has allowed qualitative analysis of the same specimen used for histopathological evaluation. Breast cancer tissues have been analysed to demonstrate the feasibility of the chemical changes taking place in the biological tissue, which can be identified precisely, and the results are reproducible. Raman analysis of tissue sections provides distinct spectra that can be used to distinguish between the nuclear grades of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. Sixty cases of breast carcinoma including DCIS and IDC and seven cases of normal breast tissues were studied employing the Raman spectroscopic technique. This study reports for the first time spectral differences between DCIS grades. It is concluded that Raman spectroscopy can objectively distinguish between DCIS and IDC grades and is non-destructive and reproducible. It should become possible in future to use Raman spectroscopy as an informative and quantitative method suitable for classification of grades and diagnosis of breast carcinoma. Copyright © 2007 John Wiley & Sons, Ltd. [source]


Vascular and Biology 03

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue S1 2002
C. Parr
Background: Hepatocyte growth factor (HGF) elicits a number of functions that are tumourigenic and known to enhance the metastatic potential of tumour cells. HGF is produced as pro-HGF and requires proteolytic activation, by HGF activator, to evoke a biological response. The HGF inhibitors, HAI-1 and HAI-2, suppress the conversion of pro-HGF, through their interaction with HGF activator. This study quantitated the expression of HGF, its receptor and its inhibitors in breast cancer. Methods: Breast cancer tissues from patients (n = 97) were obtained with background normal tissues. RNA was extracted from these tissues, and HGF, c-Met, HAI-1 and HAI-2 expression was quantified using a real-time quantitative PCR (RTQ-PCR) techniques. Results: Levels of HGF and its receptor were found to be significantly higher in breast cancer than normal background tissues. The level of HAI-1 and 2 was also seen to be higher in tumour tissues. The mean results (copy number mL,1) are given in the Table below: In addition, patients with progressive diseases had a higher level of HGF (62.7 copies mL,1), than those with stable disease (43.8 copies mL,1), over a 5-year follow-up period. Furthermore, tumour tissues from node-positive patients expressed lower HAI-2 levels (341.3 copies mL,1), than the node-negative breast cancer tissues (1021.5 copies mL,1). Conclusions: This study has shown that the quantity of HGF, c-Met, HAI-1 and HAI-2 expressed in breast cancer tissues was significantly higher than that of background breast samples, and that the level of HGF is associated with progressive disease. [source]


Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression

INTERNATIONAL JOURNAL OF CANCER, Issue 6 2009
Hiroshi Fujimoto
Abstract There is growing evidence that tumor-associated macrophages (TAMs) promote tumor growth and dissemination. Many individual reports have focused on the protumor function of molecules linked to the recruitment of macrophages, but little is known about which factor has the strongest impact on recruitment of macrophages in breast cancer. To elucidate this question, we performed RT-PCR using species-specific primers and evaluated tumoral and stromal mRNA expression of macrophage chemoattractants separately in human breast tumor xenografts. The correlation between the tumoral or stromal chemoattractant mRNA expression including monocyte chemoattractant protein-1 (MCP-1) (CCL2), MIP-1, (CCL3), RANTES (CCL5), colony-stimulating factor 1, tumor necrosis factor ,, platelet-derived growth factor (PDGF)-BB and macrophage infiltration were compared. There was significant positive correlation between stromal MCP-1 expression and macrophage number (r = 0.63), and negative correlation between tumoral RANTES expression and macrophage number (r = ,0.75). However, no significant correlation was found for the other tumoral and stromal factors. The interaction between the tumor cells and macrophages was also investigated. Tumor cell,macrophage interactions augmented macrophage-derived MCP-1 mRNA expression and macrophage chemotactic activity in vitro. Treatment of immunodeficient mice bearing human breast cancer cells with a neutralizing antibody to MCP-1 resulted in significant decrease of macrophage infiltration, angiogenetic activity and tumor growth. Furthermore, immunohistochemical analysis of human breast cancer tissue showed stromal MCP-1 had a significant correlation with relapse free survival (p = 0.029), but tumoral MCP-1 did not (p = 0.105). These findings indicate that stromal MCP-1 produced as a result of tumor,stromal interactions may be important for the progression of human breast cancer and macrophages may play an important role in this tumor,stroma interaction. © 2009 UICC. [source]


Application of differential display, with in situ hybridization verification, to microscopic samples of breast cancer tissue

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 5 2003
Ruey Ho Kao
Summary., The technique of differential display (DD) has been used widely to identify potentially interesting overexpressed or repressed genes in a variety of compared samples. When used in studying tissue samples, it inevitably confronts problems of limited amount of input material and cell-type heterogeneity. We report here the application of in situ hybridization as a method of confirmatory test for DD as well as definition of cell type expressing differential cDNA. This procedure employed material derived from a single case of human mammary, grade III, infiltrating ductal carcinoma, using free-hand microdissection, where we have compared gene expression profiles in invasive tumour with those in adjacent normal tissue. A total of 21 cDNAs were found to be differentially expressed between the two tissue types; 11 upregulated in the tumour sample and 10 upregulated in the normal sample. Six cDNAs were utilized as probes for in situ hybridization analysis of a further five cases of comparably staged breast cancer. One of these clones, 11AT1, which was found to be homologous to Hsc70, was shown to be overexpressed in tumour cells relative to adjacent normal stroma and to benign glandular epithelium in all five cases; an increase in expression was further confirmed at protein level by immunohistochemistry. The study demonstrated the applicability of in situ hybridization as a screening test in DD strategy for studying tissue material and a reasonable technique combination of identifying changes in gene expression associated with tumour development. [source]


Prognostic and predictive value of HER2/neu oncogene in breast cancer

MICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2002
Shahla Masood
Abstract Assessment of HER2/neu oncogene has been used as both a prognostic and predictive marker for breast cancer. However, the choice of the best method to assess the status of HER2/neu oncogene in breast cancer tissue remains controversial. A variety of techniques are available to detect HER2/neu gene amplification and overexpression. Tissue-based detection methods by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) offers a clear advantage over other approaches. FISH is a costly and relatively difficult assay and yet appears to be a better predictor of response to Herceptin® (Trastuzumab) therapy and patient outcome. IHC is less expensive and is easier to perform; however, it suffers from a high rate of false negativity and positivity as well as inter-observer variability among pathologists. Suggestions have been made to use IHC as a screening procedure followed by confirmation by FISH in selected cases. Considering the importance of an accurate assessment of HER2/neu oncogene in selecting therapy, a better alternative may be to use FISH as the primary testing for HER2/neu oncogene. Herceptin® therapy is associated with several side effects and is expensive. Thus, in the long term, it may be more cost-effective to use the FISH procedure and reduce the possibility of under-treatment or over-treatment of breast cancer patients. In addition, assessment of HER2/neu oncogene on every newly diagnosed early breast carcinoma may not be necessary. Metastatic lesions, when they occur, can be sampled by fine needle aspiration biopsy or core needle biopsy for assessment of HER2/Neu status. Microsc. Res. Tech. 59:102,108, 2002. © 2002 Wiley-Liss, Inc. [source]


Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopy

NMR IN BIOMEDICINE, Issue 4 2010
Beathe Sitter
Abstract Absolute quantitative measures of breast cancer tissue metabolites can increase our understanding of biological processes. Electronic REference To access In vivo Concentrations (ERETIC) was applied to high resolution magic angle spinning MR spectroscopy (HR MAS MRS) to quantify metabolites in intact breast cancer samples. The ERETIC signal was calibrated using solutions of creatine and TSP. The largest relative errors of the ERETIC method were 8.4%, compared to 4.4% for the HR MAS MRS method using TSP as a standard. The same MR experimental procedure was applied to intact tissue samples from breast cancer patients with clinically defined good (n,=,13) and poor (n,=,16) prognosis. All samples were examined by histopathology for relative content of different tissue types and proliferation index (MIB-1) after MR analysis. The resulting spectra were analyzed by quantification of tissue metabolites (,-glucose, lactate, glycine, myo-inositol, taurine, glycerophosphocholine, phosphocholine, choline and creatine), by peak area ratios and by principal component analysis. We found a trend toward lower concentrations of glycine in patients with good prognosis (1.1,µmol/g) compared to patients with poor prognosis (1.9,µmol/g, p,=,0.067). Tissue metabolite concentrations (except for ,-glucose) were also found to correlate to the fraction of tumor, connective, fat or glandular tissue by Pearson correlation analysis. Tissue concentrations of ,-glucose correlated to proliferation index (MIB-1) with a negative correlation factor (,0.45, p,=,0.015), consistent with increased energy demand in proliferating tumor cells. By analyzing several metabolites simultaneously, either in ratios or by metabolic profiles analyzed by PCA, we found that tissue metabolites correlate to patients' prognoses and health status five years after surgery. This study shows that the diagnostic and prognostic potential in MR metabolite analysis of breast cancer tissue is greater when combining multiple metabolites (MR Metabolomics). Copyright © 2010 John Wiley & Sons, Ltd. [source]


High-resolution magic angle spinning MRS of breast cancer tissue

NMR IN BIOMEDICINE, Issue 5 2002
Beathe Sitter
Abstract High-resolution magic angle spinning (HR MAS) may develop into a new diagnostic tool for studying intact tissue samples, and several types of cancer have been investigated with promising results. In this study HR MAS spectra of breast cancer tissue from 10 patients have been compared to conventional high-resolution spectra of perchloric acid extracts of the same tissue type. The HR MAS spectra show resolution comparable to spectra of extracts, and two-dimensional techniques lead to identification of a majority of the constituents. More than 30 different metabolites have been detected and assigned. To our knowledge this is the most detailed assignment of biochemical components in intact human breast tissue. The spectra of intact breast cancer tissue differ from perchloric acid extracts by the presence of lipids and fewer signals in the low field region. HR MAS analysis of intact breast tissue specimens is a rapid method, providing spectra with resolution where relative quantification of the majority of the detected metabolites is possible. Copyright © 2002 John Wiley & Sons, Ltd. [source]


Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survival

CANCER, Issue 9 2007
Chuanzhong Ye MD
Abstract BACKGROUND. The ataxia-telangiectasia mutated (ATM) gene plays a critical role in cell-cycle arrest, apoptosis, and DNA repair. However, to date, no study has directly investigated the association between ATM gene expression and breast cancer survival. METHODS. ATM gene expression levels were evaluated in tumor and adjacent normal tissue from patients diagnosed with primary breast cancer or BBD using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Cox regression models were used to evaluate the association of ATM gene expression and survival in a cohort of 471 breast cancer patients. RESULTS. In breast cancer cases, ATM expression in cancer tissues was decreased by approximately 50% compared with adjacent normal tissues from the same patients. In BBD cases, the expression level of the ATM gene was similar in benign tumor tissue and adjacent normal tissues. No apparent difference was found in ATM gene expression levels in adjacent normal tissues obtained from cancer patients or BBD controls. Compared with patients with the lowest tertile of the ATM mRNA, patients in the upper 2 tertiles had more favorable disease-free survival (hazard ratio [HR] = 0.46, 95% confidence interval [CI]: 0.30,0.73 and HR = 0.52, 95% CI: 0.33,0.81, respectively) and overall survival (HR = 0.56, 95% CI: 0.35,0.92 and HR = 0.70, 95% CI: 0.43,1.13, respectively). CONCLUSIONS. The ATM gene expression was down-regulated in breast cancer tissues and a high ATM gene expression level in breast cancer tissue was associated with a favorable prognosis. Cancer 2007. © 2007 American Cancer Society. [source]


Identification of novel alternatively spliced BRCA1-associated RING domain (BARD1) messenger RNAs in human peripheral blood lymphocytes and in sporadic breast cancer tissues

GENES, CHROMOSOMES AND CANCER, Issue 9 2007
Grazia Lombardi
BARD1 (BRCA1-associated RING domain) is the dominant binding partner of BRCA1 in vivo. The BARD1 gene has been reported to be mutated in a subset of breast and ovarian cancer patients and BARD1 germ-line mutations have been identified in breast cancer patients negative for BRCA1 or BRCA2 gene alterations. In the present study, we show by RT-PCR and direct sequencing analysis the occurrence of seven novel and one previously identified BARD1 splicing variants in human lymphocytes and breast cancers. Two of the eight variants (BARD1, and BARD1 ,RIN) preserve a correct open reading frame and could encode BARD1 internally deleted proteins, while the remaining six variants display premature stop codons. Characterization of the relative expression of BARD1 FL, BARD1,, and BARD1 ,RIN using quantitative PCR analysis indicated that the mean expression levels of BARD1 FL, BARD1,, and BARD1 ,RIN were significantly higher in tumors than in morphologically normal tissues and lymphocytes. However, we were unable to identify either qualitatively or quantitatively tumor-specific expression patterns of the identified BARD1 splicing variants. © 2007 Wiley-Liss, Inc. [source]


Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009
Seon-Ah Ha
Abstract Obese women have an increased risk for post-menopausal breast cancer. The physiological mechanism by which obesity contributes to breast tumourigenesis is not understood. We previously showed that HCCR-1 oncogene contributes to breast tumourigenesis as a negative regulator of p53 and detection of HCCR-1 serological level was useful for the diagnosis of breast cancer. In this study, we found that the HCCR-1 level is elevated in breast cancer tissues and cell lines compared to normal breast tissues. We identified apolipoprotein E (ApoE) interacting with HCCR-1. Our data show that HCCR-1 inhibits anti-proliferative effect of ApoE, which was mediated by diminishing ApoE secretion of breast cancer cells. Finally, HCCR-1 induced the severe obesity in transgenic mice. Those obese mice showed severe hyperlipidaemia. In conclusion, our results suggest that HCCR-1 might play a role in the breast tumourigenesis while the overexpression of HCCR-1 induces the obesity probably by inhibiting the cholesterol-lowering effect of ApoE. Therefore, HCCR-1 seems to provide the molecular link between the obesity and the breast cancer risk. [source]


Raman spectroscopic analysis of breast cancer tissues: identifying differences between normal, invasive ductal carcinoma and ductal carcinoma in situ of the breast tissue

JOURNAL OF RAMAN SPECTROSCOPY, Issue 10 2007
Shazza Rehman
Abstract A relatively non-destructive method employing Raman spectroscopy for the analysis of histopathological specimens is described. Raman spectroscopy has allowed qualitative analysis of the same specimen used for histopathological evaluation. Breast cancer tissues have been analysed to demonstrate the feasibility of the chemical changes taking place in the biological tissue, which can be identified precisely, and the results are reproducible. Raman analysis of tissue sections provides distinct spectra that can be used to distinguish between the nuclear grades of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. Sixty cases of breast carcinoma including DCIS and IDC and seven cases of normal breast tissues were studied employing the Raman spectroscopic technique. This study reports for the first time spectral differences between DCIS grades. It is concluded that Raman spectroscopy can objectively distinguish between DCIS and IDC grades and is non-destructive and reproducible. It should become possible in future to use Raman spectroscopy as an informative and quantitative method suitable for classification of grades and diagnosis of breast carcinoma. Copyright © 2007 John Wiley & Sons, Ltd. [source]


Quantification of glycerol diffusion in human normal and cancer breast tissues in vitro with optical coherence tomography

LASER PHYSICS LETTERS, Issue 4 2010
H.Q. Zhong
Abstract Optical coherence tomography (OCT) holds great promise as a routine research tool for analysis of identifying the boundaries between normal and diseased breast tissue in vitro and in vivo. However, despite the depth penetration afforded by this imaging modality, light attenuation in tissues imposes limitations. Here we studied the optical clearing effect of glycerol in human cancer and normal breast tissues with OCT for functional imaging to monitor. Depth- and time-resolved profiles for OCT signal enhancement were presented. The results show that the OCT imaging depth and imaging contrast of breast tissues have been improved after application of 60% glycerol in the 2-D OCT images. The OCT slope signals of breast tissues decreased as glycerol diffusion into tissues, therefore, the water and intercellular fluids were drawn out from tissues. Then the reverse process due to water was drawn back into the cells as a result of its affinity for water. The permeability coefficient of 60% glycerol was (3.14 ± 0.07) × 10,5 cm/s in breast cancer tissues, and (0.89 ± 0.02) × 10,5 cm/s in normal breast tissues, respectively. The permeability coefficient of glycerol in cancer tissues was 3.54-fold than that in normal tissues. These results demonstrate that the optical clearing of normal and cancer breast tissues are improved after application of glycerol. (© 2010 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA) [source]


The expression of SIAH1 is downregulated and associated with Bim and apoptosis in human breast cancer tissues and cells

MOLECULAR CARCINOGENESIS, Issue 5 2010
Yuan-Yuan Wen
Abstract Seven in absentia homolog1 (SIAH1) was reported as a tumor suppressor and played an important role in regulating cell apoptosis. However, its effects on the breast carcinogenesis remain unclear. In this study, our aims were to examine the relationship between SIAH1 and Bcl-2-interacting mediator of cell death (Bim) and to explore the effects of SIAH1 on the breast carcinogenesis. Immunohistochemical analysis in 231 cases of breast tissues showed that the expression of SIAH1 and Bim were significantly decreased in the breast carcinogenesis. Moreover, SIAH1 expression was significantly correlated with Bim. Both SIAH1 and Bim expression were significantly higher in well to moderately differentiated and in early-stage breast cancer. Reverse transcription (RT)-polymerase chain reaction (PCR) and Western blot analysis in paired breast cancer tissues and breast cell lines found that the expression of SIAH1 was lower in the breast cancer tissues and cell lines. SIAH1 inducing apoptosis of the breast cancer cells was dependent on Bim. However, SIAH1 inhibiting invasion of the breast cancer cells was independent of Bim. The increase of the function of SIAH1 to upregulate the expression of Bim may play an important role in the progression of breast cancer. Restoration of the function of SIAH1 may be a new therapeutic target of human breast cancer. © 2010 Wiley-Liss, Inc. [source]


In situ estrogen production and its regulation in human breast carcinoma: From endocrinology to intracrinology

PATHOLOGY INTERNATIONAL, Issue 11 2009
Hironobu Sasano
The great majority of breast carcinomas arising in postmenopausal women are estrogen dependent or positive for estrogen receptor (ER) in carcinoma cells despite markedly low plasma or circulating estrogen concentrations. In these patients, biologically active estrogens are locally produced from circulating inactive steroids including adrenal androgens in an intracrine mechanism in the breast cancer tissues and confer estrogenic activities on carcinoma cells. A series of enzymes are involved in this intra-tumoral or in situ production of estrogens in breast carcinoma tissues but aromatase, a member of the cytochrome P450 family, is a key enzyme of estrogen production through conversion from circulating adrenal androgens in estrogen-dependent postmenopausal breast cancer. It then becomes important to identify the sites of this estrogen production. There has been, however, controversy regarding intra-tumoral localization of aromatase in breast carcinoma, especially whether intra-tumoral production of estrogens through aromatase occurs in carcinoma or stromal cells. The enzyme was demonstrated to be expressed in both carcinoma and stromal cells in breast carcinoma tissues on immunohistochemistry with a well-characterized mAb 677 and combined laser capture microdissection/qualitative reverse transcriptase,polymerase chain reaction. Intra-tumoral aromatase in both of these cell types was subsequently demonstrated to be induced by carcinoma,stromal interactions associated with carcinoma invasion in breast tissue. The signals through various nuclear receptors, especially estrogen-related receptor-, in carcinoma cells and liver receptor homologue-1 in adipocytes adjacent to carcinoma invasion, in conjunction with various cytokines and/or growth factors, play pivotal roles in this induction of intra-tumoral aromatase. This increased aromatase subsequently results in increased in situ estrogen concentrations of breast cancer. Aromatase inhibitors are currently established as the gold standard for the treatment for ER-positive breast carcinoma but resistance to the therapy still remains to be solved by other modes of suppression of intra-tumoral estrogen production. [source]


Method optimisation for peptide profiling of microdissected breast carcinoma tissue by matrix-assisted laser desorption/ionisation-time of flight and matrix-assisted laser desorption/ionisation-time of flight/time of flight-mass spectrometry

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 10 2005
Arzu Umar
Abstract Appropriate methods for the analysis of microdissected solid tumour tissues by matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF MS) are not yet well established. Optimisation of sample preparation was performed first on undissected tissue slices, representing ,200,000 cells, which were solubilised either in urea containing buffer, trifluoroethanol/NH4HCO3, 0.1% sodium dodecyl sulphate (SDS) or in 0.1% RapiGest solution, then trypsin digested and analysed by MALDI-TOF MS. Solubilisation in 0.1% SDS resulted in detection of the highest number of sample specific peak signals. Interestingly, there was little overlap in detectable peaks using the different buffers, implying that they can be used complementarily to each other. Additionally, we fractionated tryptic digests on a monolithic high-performance liquid chromatography column. Fractionation of tryptic digest from whole tissue sections resulted in a four-fold increase in the total number of peaks detected. To prove this principle, we used 0.1% SDS to generate peptide patterns from 2000 microdissected tumour and stromal cells from five different breast carcinoma tumours. The tumour and stroma specific peaks could be detected upon comparison of the peptide profiles. Identification of differentially expressed peaks by MALDI-TOF/TOF MS was performed on fractionated tryptic digests derived from a whole tissue slice. In conclusion, we describe a method that is suitable for direct peptide profiling on small amounts of microdissected cells obtained from breast cancer tissues. [source]


Vascular and Biology 03

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue S1 2002
C. Parr
Background: Hepatocyte growth factor (HGF) elicits a number of functions that are tumourigenic and known to enhance the metastatic potential of tumour cells. HGF is produced as pro-HGF and requires proteolytic activation, by HGF activator, to evoke a biological response. The HGF inhibitors, HAI-1 and HAI-2, suppress the conversion of pro-HGF, through their interaction with HGF activator. This study quantitated the expression of HGF, its receptor and its inhibitors in breast cancer. Methods: Breast cancer tissues from patients (n = 97) were obtained with background normal tissues. RNA was extracted from these tissues, and HGF, c-Met, HAI-1 and HAI-2 expression was quantified using a real-time quantitative PCR (RTQ-PCR) techniques. Results: Levels of HGF and its receptor were found to be significantly higher in breast cancer than normal background tissues. The level of HAI-1 and 2 was also seen to be higher in tumour tissues. The mean results (copy number mL,1) are given in the Table below: In addition, patients with progressive diseases had a higher level of HGF (62.7 copies mL,1), than those with stable disease (43.8 copies mL,1), over a 5-year follow-up period. Furthermore, tumour tissues from node-positive patients expressed lower HAI-2 levels (341.3 copies mL,1), than the node-negative breast cancer tissues (1021.5 copies mL,1). Conclusions: This study has shown that the quantity of HGF, c-Met, HAI-1 and HAI-2 expressed in breast cancer tissues was significantly higher than that of background breast samples, and that the level of HGF is associated with progressive disease. [source]


Expression patterns of the ATM gene in mammary tissues and their associations with breast cancer survival

CANCER, Issue 9 2007
Chuanzhong Ye MD
Abstract BACKGROUND. The ataxia-telangiectasia mutated (ATM) gene plays a critical role in cell-cycle arrest, apoptosis, and DNA repair. However, to date, no study has directly investigated the association between ATM gene expression and breast cancer survival. METHODS. ATM gene expression levels were evaluated in tumor and adjacent normal tissue from patients diagnosed with primary breast cancer or BBD using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Cox regression models were used to evaluate the association of ATM gene expression and survival in a cohort of 471 breast cancer patients. RESULTS. In breast cancer cases, ATM expression in cancer tissues was decreased by approximately 50% compared with adjacent normal tissues from the same patients. In BBD cases, the expression level of the ATM gene was similar in benign tumor tissue and adjacent normal tissues. No apparent difference was found in ATM gene expression levels in adjacent normal tissues obtained from cancer patients or BBD controls. Compared with patients with the lowest tertile of the ATM mRNA, patients in the upper 2 tertiles had more favorable disease-free survival (hazard ratio [HR] = 0.46, 95% confidence interval [CI]: 0.30,0.73 and HR = 0.52, 95% CI: 0.33,0.81, respectively) and overall survival (HR = 0.56, 95% CI: 0.35,0.92 and HR = 0.70, 95% CI: 0.43,1.13, respectively). CONCLUSIONS. The ATM gene expression was down-regulated in breast cancer tissues and a high ATM gene expression level in breast cancer tissue was associated with a favorable prognosis. Cancer 2007. © 2007 American Cancer Society. [source]