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Breast Cancer Progression (breast + cancer_progression)
Selected AbstractsThe lim domain only protein 7 is important in zebrafish heart developmentDEVELOPMENTAL DYNAMICS, Issue 12 2008Elisabeth B. Ott Abstract The LIM domain only protein 7 (LMO7), a member of the PDZ and LIM domain-containing protein family is a candidate gene with possible roles in embryonic development and breast cancer progression. LMO7 has been linked to actin cytoskeleton organization through nectin/afadin and to cell,cell adhesion by means of E-cadherin/catenin. In addition, LMO7 has been shown to regulate transcription of the nuclear membrane protein Emerin and other muscle relevant genes. In this study, we used in situ hybridization to investigate LMO7 expression during embryonic development in three widely used vertebrate model species: the zebrafish, the chicken and the mouse. Our temporal and spatial gene expression analysis revealed both common and distinct patterns between these species. In mouse and chicken embryos we found expression in the outflow tract, the inflow tract, the pro-epicardial organ and the second heart field, structures highly important in the developing heart. Furthermore, gene knockdown experiments in zebrafish embryos resulted in severe defects in heart development with effects on the conduction system and on heart localization. In summary, we present here the first developmental study of LMO7. We reveal the temporal and spatial expression patterns of this important gene during mouse, chicken and fish development and our findings suggest essential functions for LMO7 during vertebrate heart development. Developmental Dynamics 237:3940,3952, 2008. © 2008 Wiley-Liss, Inc. [source] ERBB2, TBX2, RPS6KB1, and MYC alterations in breast tissues of BRCA1 and BRCA2 mutation carriersGENES, CHROMOSOMES AND CANCER, Issue 1 2004Camilo Adem Breast cancer risk is greatly increased in women who carry mutations in the BRCA1 or BRCA2 genes. Because breast cancer initiation is different between BRCA1/2 mutation carriers and women who do not carry mutations, it is possible that the mechanism of breast cancer progression is also different. Histopathologic and genetic studies have supported this hypothesis. To test this hypothesis further, we utilized a large cohort of women who underwent therapeutic mastectomy (TM) and contralateral prophylactic mastectomy (PM). From this cohort, we developed case groups of women with a family history of breast cancer with BRCA1/2 deleterious mutations, with unclassified variant alterations, and with no detected mutation and matched these cases with sporadic controls from the same TM and PM cohort. Fluorescence in situ hybridization was performed on paraffin sections by use of dual-color probes for ERBB2/CEP17, MYC/CEP8, TBX2/CEP17, and RPS6KB1/CEP17. All malignant and benign lesions, including putative precursor lesions, were studied. The invasive cancers from deleterious mutation carriers had a higher prevalence of duplication of MYC (P = 0.006) and TBX2 (P = 0.0008) compared to controls and a lower prevalence of ERBB2 amplification (P = 0.011). Coduplication of MYC and TBX2 was common in the in situ and invasive lesions from the deleterious mutation carriers. The odds ratio of having a BRCA1/2 mutation is 31.4 (95% CI = 1.7,569) when MYC and TBX2 are coduplicated but ERBB2 is normal. Unclassified variant carriers/no mutation detected and sporadic controls had a similar prevalence of alterations, suggesting that hereditary patients with no deleterious mutations follow a progression pathway similar to that of sporadic cases. With the exception of one atypical ductal hyperplasia lesion, no putative precursor lesion showed any detectable alteration of the probes tested. There was no significant intratumoral heterogeneity of genetic alterations. Our data confirm that a specific pattern of genomic instability characterizes BRCA1/2 -related cancers and that this pattern has implications for the biology of these cancers. Moreover, our current and previous results emphasize the interaction between phenotype and genotype in BRCA1/2 -related breast cancers and that a combination of morphologic features and alterations of ERBB2, MYC, and TBX2 may better define mechanisms of tumor progression, as well as determine which patients are more likely to carry BRCA1/2 mutations. © 2004 Wiley-Liss, Inc. [source] Induction of acquired resistance to antiestrogen by reversible mitochondrial DNA depletion in breast cancer cell lineINTERNATIONAL JOURNAL OF CANCER, Issue 7 2008Akihiro Naito Abstract Although the net benefits of tamoxifen in adjuvant breast cancer therapy have been proven, the recurrence of the cancer in an aggressive and hormone independent form has been highly problematic. We previously demonstrated the important role mitochondrial DNA (mtDNA) plays in hormone-independence in prostate cancer. Here, the role of mtDNA in breast cancer progression was investigated. We established hydroxytamoxifen (4-OHT) resistant HTRMCF by growing MCF-7, human breast adenocarcinoma cells, in the presence of 4-OHT. HTRMCF was cross-resistant to 4-OHT and ICI182,780 concurrent with the depletion of mtDNA. To further investigate the role of mtDNA depletion, MCF-7 was depleted of mtDNA by treatment with ethidium bromide. MCF,0 was resistant to both 4-OHT and ICI182,780. Furthermore, cybrid (MCFcyb) prepared by fusion MCF,0 with platelet to transfer mtDNA showed susceptibility to antiestrogen. Surprisingly, after withdrawal of 4-OHT for 8 weeks, HTRMCF and their clones became susceptible to both drugs concurrent with a recovery of mtDNA. Herein, our results substantiated the first evidence that the depletion of mtDNA induced by hormone therapy triggers a shift to acquired resistance to hormone therapy in breast cancer. In addition, we showed that mtDNA depletion can be reversed, rendering the cancer cells susceptible to antiestrogen. The fact that the hormone independent phenotype can be reversed should be a step toward more effective treatments for estrogen-responsive breast cancer. © 2007 Wiley-Liss, Inc. [source] Defining ETS transcription regulatory networks and their contribution to breast cancer progressionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2007David P. Turner Abstract ETS factors are members of one of the largest families of evolutionarily conserved transcription factors, regulating critical functions in normal cell homeostasis, that when perturbed contribute to tumor progression. The well documented alterations in ETS factor expression and function during breast cancer progression result in pleiotropic effects manifested by the downstream effect on their target genes. Multiple ETS factors bind to the same regulatory sites present on target genes, suggesting redundant or competitive functions. Furthermore, additional events contribute to, or may be necessary for, target gene regulation. In order to advance our understanding of the ETS-dependent regulation of breast cancer progression and metastasis, this prospect article puts forward a model for examining the effects of simultaneous expression of multiple transcription factors on the transcriptome of non-metastatic and metastatic breast cancer. Compared to existing RNA profiles defined following expression of individual transcription factors, the anti- and pro-metastatic signatures obtained by examining specific ETS regulatory networks will significantly improve our ability to accurately predict tumor progression and advance our understanding of gene regulation in cancer. Coordination of multiple ETS gene functions also mediates interactions between tumor and stromal cells and thus contributes to the cancer phenotype. As such, these new insights may provide a novel view of the ETS gene family as well as a focal point for studying the complex biological control involved in tumor progression. J. Cell. Biochem. 102: 549,559, 2007. © 2007 Wiley-Liss, Inc. [source] Shepherding AKT and androgen receptor by Ack1 tyrosine kinaseJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Kiran Mahajan Ack1 (also known as ACK, TNK2, or activated Cdc42 kinase) is a structurally unique non-receptor tyrosine kinase that is expressed in diverse cell types. It integrates signals from plethora of ligand-activated receptor tyrosine kinases (RTKs), for example, MERTK, EGFR, HER2, PDGFR and insulin receptor to initiate intracellular signaling cascades. Ack1 transduces extracellular signals to cytosolic and nuclear effectors such as the protein kinase AKT/PKB and androgen receptor (AR), to promote cell survival and growth. While tyrosine phosphorylation of AR at Tyr267 regulates androgen-independent recruitment of AR to the androgen-responsive enhancers and transcription of AR target genes to drive prostate cancer progression, phosphorylation of an evolutionarily conserved Tyrosine 176 in the kinase domain of AKT is essential for mitotic progression and positively correlates with breast cancer progression. In contrast to AR and AKT, Ack1-mediated phosphorylation of the tumor suppressor Wwox at Tyr287 lead to rapid Wwox polyubiquitination followed by degradation. Thus, by its ability to promote tumor growth by negatively regulating tumor suppressor such as Wwox and positively regulating pro-survival factors such as AKT and AR, Ack1 is emerging as a critical player in cancer biology. In this review, we discuss recent advances in understanding the physiological functions of Ack1 signaling in normal cells and the consequences of its hyperactivation in various cancers. J. Cell. Physiol. 224: 327,333, 2010. © 2010 Wiley-Liss, Inc. [source] Her2V655 genotype and breast cancer progression in Korean womenPATHOLOGY INTERNATIONAL, Issue 2 2005Hee Jung An The amplification and overexpression of Her2 proto-oncogene have been found to be associated with the development and progression of human breast cancer. A polymorphic valine allele at codon 655 of the Her2 gene (Her2V655) was suggested by some authors to be a susceptible genetic factor for the development of breast cancer. The Her2 polymorphism at codon 655 was investigated in 304 Korean women including 177 patients with breast cancer. The association between Her2 genotype and Her2 protein overexpression was also examined in breast cancers by immunohistochemistry. Her2V655 was not associated with a significant breast cancer risk (odds ratio (OR), 1.792; 95% confidence interval (CI), 0.459,6.991). The frequency of homozygous or heterozygous valine allele increased in stage 2 patients (OR, 1.67; 95% CI, 0.67,4.19), and patients in stages 3 and 4 (OR, 3.36; 95% CI, 0.85,13.42) compared to patients in stage 0. However, an association between the presence of the valine allele and the overexpression of Her2 protein could not be demonstrated. These results suggest that Her2 polymorphism at codon 655 is not associated with the development of breast cancer in Korean women. However, there is a possibility that the valine allele at codon 655 might be related to increased risk of breast cancer progression. [source] | |||||||||||||