Home  About us  Contact
 

Human Lung Adenocarcinoma (human + lung_adenocarcinoma)

Distribution by Scientific Domains
Medical Sciences87%

Selected Abstracts

Inactivation of O6 -Methylguanine-DNA Methyltransferase in Human Lung Adenocarcinoma Relates to High-grade Histology and Worse Prognosis among Smokers

CANCER SCIENCE, Issue 2 2002
Hiroyuki Hayashi
To evaluate the significance of O6 -methylguanine-DNA methyltransferase (MGMT) activity in the development of human lung adenocarcinoma (AC), we investigated promoter hypermethylation of the MGMTx gene by methylation-specific PCR, and the expression of MGMT protein by immuno-histochemistry in relation to smoking history of the patients. In total, 31 of 87 AC patients (35.5%) showed hypermethylation of the MGMT gene, and no significant difference was observed between smokers (37.3%) and non-smokers (33.3%). However, hypermethylation of the MGMT gene increased in parallel with lesser differentiation grade of tumors among smokers (well, 16.7%; moderately, 42.1%; poorly, 57.1%; P=0.022), although this trend was not observed among non-smokers. Almost all the tumors with promoter hypermethylation of the MGMT gene showed consistently negative MGMT staining by immunohistochemistry. When the prognosis of stage-I patients was compared among smokers, it was apparent that the prognosis of patients with inactivated MGMT was worse than that of MGMT-positive patients (P=0.036). Such differences in the prognoses were not observed among non-smokers. In conclusion, MGMT inactivation is related to the differentiation grade and the prognosis of lung AC patients among smokers. Although further studies are required, we speculate that smoking may induce hypermethylation, not only of the MGMT gene, but also of other important tumor suppressor genes. [source]

Establishment of Cell Lines with High- and Low-metastatic Potential from PC-14 Human Lung Adenocarcinoma

CANCER SCIENCE, Issue 2 2001
Nobuko Shindo-Okada
This article reports the establishment of variant cell lines with high and low metastatic potential by repeated selection and the dilution plating technique. Five clones with high metastatic potential, Lu-2, Lu-7, Lu-4, Lu-1 and Lu-5, and four clones with low metastatic potential, 3S, 7S, 8S and 13S, were established from PC-14 human lung adenocarcinoma. The high-metastatic cell lines produced enhanced lung metastases, but the low-metastatic cell lines did not produce lung metastasis by injection into the tail vein of 5-week-old BALB/c nude mice. The high-metastatic cell lines produced enhanced tumors on both visceral and parietal pleurae, and enhanced metastases to the mediastinum and contralateral pleural cavity. The low-metastatic cell lines produced reduced tumors on both visceral and parietal pleurae and reduced metastases to the mediastinum and contralateral pleural cavity after injection into the left preceral cavity of the nude mice. When the nine variant cell lines and original PC-14 cells were embedded in collagen gels, the PC-14 cells and the low-metastatic cell lines gave rise to colonies with a dendritic morphology, and cells were tightly associated. The high-metastatic cell lines were more loosely associated and scattered into three-dimensional colonies. These nine cloned cell lines originated from heterogeneous populations of the parental PC-14 cells should be useful tools for studying the process of metastasis of lung cancer. [source]

Mutational activation of the MAP3K8 protooncogene in lung cancer

GENES, CHROMOSOMES AND CANCER, Issue 2 2004
Adam Michael Clark
The MAP3K8 protooncogene (Cot/Tpl-2) activates the MAP kinase, SAP kinase, and NF-,B signaling pathways. MAP3K8 mutations occur in the rat homologue, but activating mutations have yet to be identified in primary human tumors. We have identified MAP3K8 as a transforming gene from a human lung adenocarcinoma and characterized a 3, end mutation in the cDNA. In addition, we confirmed that the mutation occurs in the original lung tumor, and we screened a series of lung cancer cell lines to determine whether the MAP3K8 mutation is a common occurrence in lung tumorigenesis. The oncogene was isolated and identified with the NIH3T3 nude mouse tumorigenicity assay and cDNA library screening. The gene was analyzed by polymerase chain reaction (PCR), single-strand conformational polymorphism (SSCP), and 3,RACE for mutations. The mutation was localized to MAP3K8 exon 8 and confirmed in the primary tumor DNA. Both wild-type and mutant MAP3K8 cDNAs transformed NIH3T3 cells, but the transforming activity of the mutant was much greater than that of the wild type. PCR-SSCP screening of cell line cDNAs identified one silent polymorphism in cell line SK-LU-1. Although we were unable to find additional activating mutations, these data support a role for MAP3K8 activity in cellular transformation, but suggest that mutational activation of the gene is a rare event in lung cancer. © 2004 Wiley-Liss, Inc. [source]

Frequent aberrant methylation of the promoter region of sterile , motif domain 14 in pulmonary adenocarcinoma

CANCER SCIENCE, Issue 11 2008
Weihong Sun
Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor-suppressor and tumor-related genes. In order to identify novel hypermethylated genes in early stage lung adenocarcinoma, we carried out methylated CpG island amplification, modified suppression subtractive hybridization, and methylation-specific polymerase chain reaction to identify aberrant methylation of CpG islands in the A/J mouse lung adenoma model, which histologically mimics the early stage of human pulmonary adenocarcinoma. Through methylated CpG island amplification, suppression subtractive hybridization, and differential screening, we detected five genes, three of which have human homologs. Two of them showed downregulation of their expression in human lung adenocarcinoma. Of these two genes, we selected sterile , motif domain 14 (SAMD14) and further analyzed its methylation status and expression level by methylation-specific polymerase chain reaction and quantitative real-time polymerase chain reaction. Most of the lung adenocarcinoma cell lines showed suppressed expression of SAMD14 together with hypermethylation at the promoter region, although an immortalized bronchial epithelium cell line (PL16B) did not show hypermethylation and did express SAMD14. The expression of SAMD14 in A549 was rescued by treatment with the demethylation agent 5-aza-2,-deoxycytidine. These data indicate that hypermethylation of the SAMD14 gene promoter region is associated with silencing of its expression. Hypermethylation at the CpG site of the SAMD14 promoter region was detected frequently in early invasive adenocarcinoma (8/24, 33.3%) but not in in situ adenocarcinoma (0/7, 0%) or normal lung tissue (0/31, 0%). Hypermethylation of the SAMD14 gene is a specific event in pulmonary adenocarcinogenesis and malignant progression. (Cancer Sci 2008; 99: 2177,2184) [source]

Inactivation of O6 -Methylguanine-DNA Methyltransferase in Human Lung Adenocarcinoma Relates to High-grade Histology and Worse Prognosis among Smokers

CANCER SCIENCE, Issue 2 2002
Hiroyuki Hayashi
To evaluate the significance of O6 -methylguanine-DNA methyltransferase (MGMT) activity in the development of human lung adenocarcinoma (AC), we investigated promoter hypermethylation of the MGMTx gene by methylation-specific PCR, and the expression of MGMT protein by immuno-histochemistry in relation to smoking history of the patients. In total, 31 of 87 AC patients (35.5%) showed hypermethylation of the MGMT gene, and no significant difference was observed between smokers (37.3%) and non-smokers (33.3%). However, hypermethylation of the MGMT gene increased in parallel with lesser differentiation grade of tumors among smokers (well, 16.7%; moderately, 42.1%; poorly, 57.1%; P=0.022), although this trend was not observed among non-smokers. Almost all the tumors with promoter hypermethylation of the MGMT gene showed consistently negative MGMT staining by immunohistochemistry. When the prognosis of stage-I patients was compared among smokers, it was apparent that the prognosis of patients with inactivated MGMT was worse than that of MGMT-positive patients (P=0.036). Such differences in the prognoses were not observed among non-smokers. In conclusion, MGMT inactivation is related to the differentiation grade and the prognosis of lung AC patients among smokers. Although further studies are required, we speculate that smoking may induce hypermethylation, not only of the MGMT gene, but also of other important tumor suppressor genes. [source]

Establishment of Cell Lines with High- and Low-metastatic Potential from PC-14 Human Lung Adenocarcinoma

CANCER SCIENCE, Issue 2 2001
Nobuko Shindo-Okada
This article reports the establishment of variant cell lines with high and low metastatic potential by repeated selection and the dilution plating technique. Five clones with high metastatic potential, Lu-2, Lu-7, Lu-4, Lu-1 and Lu-5, and four clones with low metastatic potential, 3S, 7S, 8S and 13S, were established from PC-14 human lung adenocarcinoma. The high-metastatic cell lines produced enhanced lung metastases, but the low-metastatic cell lines did not produce lung metastasis by injection into the tail vein of 5-week-old BALB/c nude mice. The high-metastatic cell lines produced enhanced tumors on both visceral and parietal pleurae, and enhanced metastases to the mediastinum and contralateral pleural cavity. The low-metastatic cell lines produced reduced tumors on both visceral and parietal pleurae and reduced metastases to the mediastinum and contralateral pleural cavity after injection into the left preceral cavity of the nude mice. When the nine variant cell lines and original PC-14 cells were embedded in collagen gels, the PC-14 cells and the low-metastatic cell lines gave rise to colonies with a dendritic morphology, and cells were tightly associated. The high-metastatic cell lines were more loosely associated and scattered into three-dimensional colonies. These nine cloned cell lines originated from heterogeneous populations of the parental PC-14 cells should be useful tools for studying the process of metastasis of lung cancer. [source]

Intracellular presence of insulin and its phosphorylated receptor in non-small cell lung cancer,

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2009
Stefano Mattarocci
Insulin has been known for a long time to influence the growth and differentiation of normal and transformed cells. In order to delineate the role of insulin specifically in non-small cell lung cancer (NSCLC), we have now searched by immunohistochemistry (IHC) for the presence of insulin in NSCLC samples. Among the 112 samples we studied, 30 were found to contain insulin, which was detected in the form of intracytoplasmic granula. Moreover, its expression significantly correlated with (a) the morphological/histopathological subtype of NSCLC, being more frequent in adenocarcinomas; (b) the grade of tumor differentiation, displaying an increase in low-grade carcinomas; (c) tumor size, occurring predominantly in smaller tumors; (d) the presence of phosphorylated, activated insulin receptor; (e) the median patient age, being present in relatively younger individuals. Furthermore and interestingly, surrounding atypical adenomatous hyperplastic areas and normal alveolar pneumocytes scored insulin-positive in some of the insulin-negative tumors. In addition, PCR exploration for insulin transcripts in some samples positive for immunoreactive insulin was negative, indicating a possibly exogenous origin for the intracellular insulin in our NSCLC cohort. Taken together, our data suggest that an intracellular insulin activity is important for the progression of low-grade human lung adenocarcinomas. J. Cell. Physiol. 221: 766,770, 2009. © 2009 Wiley-Liss, Inc. [source]

Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma

MOLECULAR CARCINOGENESIS, Issue 4 2001
Masakazu Kohda
Abstract Genomic imprinting is a parental origin,specific chromosomal modification that causes differential expression of maternal and paternal alleles of a gene. Accumulating evidence suggests that deregulation of imprinted genes, including loss of imprinting (LOI), plays a role in oncogenesis. In the present study, we investigated allelic expression of six imprinted genes in human lung adenocarcinomas as well as in matched normal lung tissue. Informative cases showing heterozygosity for the gene of interest were selected from 35 patients. LOI of the insulin-like growth factor 2 gene (IGF2) and mesoderm-specific transcript (MEST, also known as paternally expressed gene 1) was noted in 47% (seven of 15) and 85% (11 of 13) of informative cases, respectively. Monoallelic expression was maintained in all the matched normal tissues examined. LOI of IGF2 was seen more frequently in moderately to poorly differentiated adenocarcinomas. In contrast, H19, small nuclear ribonucleoprotein,associated polypeptide N gene (SNRPN), necdin gene (NDN), and long QT intronic transcript 1 (LIT1) exhibited consistent monoallelic expression in all the informative samples. These findings indicated that independent deregulation took place in imprinted genes and suggested that aberrant imprinting of IGF2 and MEST was involved in the development of lung adenocarcinoma. © 2001 Wiley-Liss, Inc. [source]