Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using single-strand conformation polymorphism we have found two polymorphic sites, AAC to AAT at codon 511 (exon 12) and GCT to GCG at codon 708 (exon 15), in the MCC gene. These sites and an RsaI polymorphic site in APC allowed us to study 23 human small cell lung cancer (SCLC) and 7 non-small cell lung cancer samples for allele loss. Of the 23 SCLC samples, 21 (91%) were informative for one or more of these markers, and we found allele loss in more than 80% (17 of 21). In non-small cell lung cancer samples, 5 of 7 (71%) were informative, and reduction or loss of one allele was found in 2 of 5 (40%). Seven cases were informative for both genes, loss of heterozygosity occurred for both genes in five, one retained heterozygosity for both, and one SCLC had loss of heterozygosity for APC but not for MCC. We conclude that loss of heterozygosity occurs frequently for MCC and APC in lung cancer of all histological types and is very frequent in SCLC. This suggests the presence of tumor suppressor gene(s) in the MCC/APC region of 5q21 involved in human lung cancer.
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PMID:Polymorphic sites within the MCC and APC loci reveal very frequent loss of heterozygosity in human small cell lung cancer. 134 17

The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity of APC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on 5q including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers. They imply that inactivation of APC, MCC, and/or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract, as well as in colon cancer and familial adenomatous polyposis.
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PMID:Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. 156 31

We have prepared a monoclonal antibody directed against human thrombomodulin. We used the antibody to measure thrombomodulin molecules in cultured human endothelial cells from umbilical vein and in a human lung cancer cell line (A549). Endothelial cells contain approximately 30,000-55,000 molecules of thrombomodulin/cell while the A549 cell has about 1/4 of this number. About 50-60% of thrombin binding sites on endothelial cells are thrombomodulin, while about 90% of thrombin binding sites on A549 cells are thrombomodulin. Exposure of these cells to thrombin decreased thrombomodulin on the cell surface suggesting that internalization of thrombin-thrombomodulin occurred. The internalized 125I-thrombin was degraded in the cells and thrombomodulin reappeared on the cell surface after 30 min, suggesting the recycling of thrombomodulin. The rate of protein C activation correlated with the presence of the thrombin-thrombomodulin complex on the cell surface. The binding of thrombin to cell-surface thrombomodulin accelerates protein C activation; the subsequent internalization of the thrombin-thrombomodulin complex is associated with cessation of protein C activation. Therefore, endocytosis of thrombin-thrombomodulin may serve to control protein C activation. The uptake and degradation of thrombin bound to thrombomodulin may provide a mechanism for clearance of thrombin from the circulation.
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PMID:The turnover of thrombin-thrombomodulin complex in cultured human umbilical vein endothelial cells and A549 lung cancer cells. Endocytosis and degradation of thrombin. 299 16

We investigated the effect of protein C on the endocytosis of thrombin-thrombomodulin complexes. We previously showed that exposure of umbilical vein endothelial cells to thrombin stimulated the internalization and degradation of thrombin. A similar internalization was stimulated by a monoclonal antithrombomodulin antibody. We have repeated these studies in the presence of protein C and found that endocytosis of 125I-thrombin-thrombomodulin complexes, but not 125I-antithrombomodulin-thrombomodulin complexes, is inhibited. Activated protein C did not inhibit endocytosis of thrombin-thrombomodulin complexes. Protein C inhibited both internalization and degradation of 125I-thrombin and diisopropylphosphoryl (DIP) 125I-thrombin in human lung cancer cells (A549). These effects were observed at protein C concentrations found in human plasma. Protein S had no effect on the inhibition of endocytosis of thrombin-thrombomodulin complexes by protein C. We propose that protein C may regulate the rate of endocytosis of thrombin-thrombomodulin complexes in vivo and thereby control the capacity for endothelium to activate protein C.
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PMID:Protein C inhibits endocytosis of thrombin-thrombomodulin complexes in A549 lung cancer cells and human umbilical vein endothelial cells. 303 8

beta-Catenin has emerged as an important component of the adherens junctions between epithelial cells. As a result of studies of its interaction with the APC gene product, it has been implicated in the development of colorectal cancer. alpha-Catenin, beta-catenin, E-cadherin and APC appear to mediate contact inhibition in epithelia. As part of the study of the organization of the beta-catenin gene, we have isolated yeast artificial chromosomes (YACs) to characterize its intron/exon structure. YAC fluorescence in situ hybridization analysis and polymerase chain reaction analysis of somatic cell hybrid DNAs show that beta-catenin maps in the 3p21-22 region, the location of tumour-suppressor genes deleted in small-cell lung cancer (SCLC) and other disorders. beta-Catenin YACs will provide a source of microsatellite markers useful in loss of heterozygosity studies to assess the importance of beta-catenin deletions in SCLC.
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PMID:Yeast artificial chromosome cloning of the beta-catenin locus on human chromosome 3p21-22. 778 Jun 64

Lung cancers exhibit multiple genetic lesions including mutations activating the dominant cellular proto-oncogenes as well as those inactivating the recessive or "tumor suppressor" genes. Candidate tumor suppressor genes include those on chromosomes 1p, 1q, 3p14, 3p21.3, 3p25 (VHL gene), 5q21 (APC/MCC gene cluster), 9p21-22 (interferon gene cluster), 11p, 13q (rb gene), 16p24, and 17p (p53 gene). Mutations in p53 inactivate its transcriptional activity, while replacement of a wild-type p53 in lung cancer cells inhibits growth and tumorigenicity suggesting that p53 acts as a master growth regulatory switch. Lung cancer cells exhibit several positive autocrine growth factor loops and express nicotine receptors which could function as tumor promoting systems. In addition, they express a negative autocrine loop involving opioids and their receptors which is reversed by nicotine acting through nicotinic acetylcholine receptors. The presence of nicotine receptors suggests nicotine or its metabolites may play a direct role in lung cancer pathogenesis.
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PMID:The molecular biology of lung cancer pathogenesis. 846 39

Germline mutations of the adenomatous polyposis coli gene are associated with the dominantly inherited syndrome of familial adenomatous polyposis. Somatic mutations in this gene are an early event in sporadic colorectal tumorigenesis. Here we report a family with genetic characteristics that do not conform exactly to either of these situations. The index case and three siblings presented with colorectal cancer, and another sibling had lung cancer. There was no evidence of colorectal cancer susceptibility in previous generations, although one case of gastric cancer was observed. Using restriction fragment length polymorphism, single-strand conformational polymorphism, and sequencing analysis, we screened each living family member for alterations in the mutation cluster region of exon 15 of the APC gene. A constitutional single base pair substitution at codon 1317 was observed in two of the siblings with colorectal cancer, but neither exhibited any colonic features typical of FAP nor an early onset of cancer. This constitutional change is a missense mutation and therefore does not result in the truncation of the APC protein, the most commonly observed result of mutation in this gene. We present evidence that this change is not a polymorphism and may be capable of conferring a growth advantage. This particular germline APC mutation does not completely cosegregate with cancer in this family; therefore, we conclude that another gene locus may be responsible for the increased cancer risk observed.
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PMID:Germline APC mutation (Gln1317) in a cancer-prone family that does not result in familial adenomatous polyposis. 883 76

I reviewed the change of respiratory medicine in the past several decades, overlapping with my own history of medical training and clinical and research works. In the 1950's when I graduated from the medical school and internship, the tuberculosis had been conquered effectively by the development of new antituberculous agents and improvement of nutritional state in Japan. Fibroptic bronchoscopy was introduced in the respiratory medicine in 1968, and computed tomography, in the 1970's, which gave us a good insight into pathological and biological aspects of various lung diseases in vivo. Molecular biology was brought in the respiratory medicine and our laboratory in the last decade, and my colleagues used it for genetic study of hereditary diseases such as alpha-1 antitrypsin deficiency and protein C deficiency, biochemical analysis of lung cancer and other pulmonary diseases, rapid detection of microorganisms, and so on. In the next step, gene therapy will come true in the near future, and I hope many intractable diseases such as lung cancer and interstitial pneumonia will be cured by the new technology and scientific knowledge.
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PMID:[Introduction of molecular biology in respiratory medicine and its perspective]. 883 70

Although the initial chemo-radiotherapy is relatively effective, lung cancer, especially small cell lung cancer (SCLC) usually becomes resistant for the therapy and gets higher grade of the malignant phenotype. The common genetic abnormalities, such as 3p deletion and mutational inactivation of p53 and Rb gene, have been well known. However, these abnormalities seem to be involved in the development of lung cancer because they could be detected at the early stage or even in the preneoplastic lesion. By means of loss of heterozygosity (LOH), we have determined two regions which are frequently lost in advanced lung cancer, 5q21 and 5q33-35. In previous reports, the low frequency of 5q loss in lung cancer has been shown in masses obtained at early but not advanced stages. Furthermore, we have found that one SCLC case showed a 5q deletion only in metastatic site but not in the primary lesion. These findings suggest that the inactivation of putative tumor suppressor gene(s) on 5q may play an important role for the progression of lung cancer. In 5q21 area, commonly deleted region was estimated to be 3 Mb around APC gene. This region was covered with several YAC clones and some cosmid contigs were constructed from these YAC clones. Two kinds of transcriptional units have been isolated from these contigs by exon-trapping, cross-species hybridization or northern blotting, so far. Since these cDNAs do not show significant homology with any known gene, their function cannot be estimated. We are trying to isolate full length cDNAs and to determine the functional and structural abnormalities in lung cancer at present.
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PMID:[Search for the tumor-suppressor gene(s) on chromosome 5q, which may play an important role for the progression of lung cancer]. 883 1

Four genetic polymorphisms in the APC and MCC genes at chromosome 5q21 were analysed for loss of heterozygosity (LOH) in 97 primary squamous carcinomas and adenocarcinomas of the lung. LOH was identified in at least two polymorphic loci in 41 percent of informative cases. There was no significant difference in the frequency of LOH between squamous carcinomas and adenocarcinomas. Within the adenocarcinoma group, however, LOH appeared to be more common in tumours having a bronchial origin (5/9; 56 per cent) than in parenchymal adenocarcinoma (6/21; 29 per cent). All 32 tumours showing LOH at one or more polymorphic sites were examined for mutations in the mutation cluster region (MCR) of APC by single-strand conformational polymorphism (SSCP) analysis. Mutations were not detected in any of these cases. We therefore propose that it is likely that a tumour suppressor gene on 5q other than APC is involved in the pathogenesis of lung cancer.
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PMID:Loss of heterozygosity at 5q21 in non-small cell lung cancer: a frequent event but without evidence of apc mutation. 894 12


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