Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical importance of ras oncogene product p21 was evaluated in surgically treated non-small cell lung cancer patients. Paraffin sections of tumors were analysed immunohistochemically using anti-ras p21 monoclonal antibody rp35. The ras p21 expression was correlated with clinicopathological parameters and survival. Survival analysis demonstrated significantly longer survival times in patients with p21-negative tumors than those with p21-positive tumors. In Cox's multivariate analysis, ras p21 expression was a major and independent prognostic determinant of survival. On the other hand, in small cell lung cancer, L-myc gene is known to be frequently amplified and overexpressed. Immunoprecipitation analysis of two small cell lung cancer cell lines (classic type) revealed three major L-myc proteins (p60, p66 and p68), all of which were derived from extensive phosphorylation of a p59 protein. Expression and phosphorylation of L-myc protein, as well as the autocrine growth mechanism of gastrin-releasing peptide (GRP), is thought to be involved in the malignant behavior of small cell lung cancer.
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PMID:[Clinical significance of oncogene product expression in human lung cancer]. 133 97

The 5-year survival of lung cancer patients is about 30% in Japan. One of the reasons for the poor prognosis seems to be drug resistance. It has been reported that certain types of oncogenes, such as ras, myc and fos, may play an important role in drug resistance. The myc protein forms a sequence-specific DNA-binding complex with Max and may act as a transcription factor; thus, it may be possible that myc family oncogenes are involved in DNA synthesis and repair processes mediating drug resistance. We report here that L-myc oncogene may be involved in the transition from drug-sensitive to drug-resistant phenotype of a certain small cell lung cancer cell line.
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PMID:[Relationship between drug resistance and oncogenes in lung cancer cell lines]. 133 94

Small cell lung cancer (SCLC) manifests a number of neuroendocrine differentiation features and antigenic characteristics that distinguish the tumour from non-small cell lung cancer (NSCLC). Several surface antigens on SCLC cells, identified by clusters of monoclonal antibodies (MAbs), distinguish SCLC and other neuroendocrine tumours of NSCLC. Stable transfection of the c-myc proto-oncogene has been reported to confer upon classic SCLC cells the growth properties and morphology of the variant subtype of SCLC (SCLC-v). Furthermore, insertion of the v-Ha-ras oncogene into such SCLC-v cells has been found to induce features typical of NSCLC. We have used classic SCLC cells transfected with c-myc, or co-transformed with c-myc and v-Ha-ras, to examine the expression of characteristics SCLC cluster antigens. Flow cytometric assays reveal that SCLC cells co-transformed with c-myc and v-Ha-ras oncogenes down-modulate SC-1, SC-2 and SC-5A surface antigens to levels approaching, in some cases, those seen with NSCLC cells. The SC-4 surface antigen is not modulated by activation of these oncogenes. These findings support clinical and laboratory observations that important transitions can occur between subtypes of human lung cancer cells, and that these shifts may play a role in the clinical progression of lung cancer.
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PMID:Modulation of neuroendocrine surface antigens in oncogene-activated small cell lung cancer lines. 164 69

The mechanism(s) by which the c-myc nuclear protein and the membrane-associated ras protein interact to mediate phenotypic changes is unknown. We now find that c-mcy gene expression is associated with alterations in the principal signal transduction pathway through which the ras protein is thought to function. We studied the transcript and protein expression of protein kinase C (PKC) isoforms in a culture line of human small cell lung cancer cells (NCI H209) in which expression of inserted c-myc and Ha-ras genes together, but not alone, causes a transition to a large cell phenotype. In control H209 cells, at the transcript and cell membrane protein levels, PKC-alpha is the dominant PKC species. In this cell line, the expression of an exogenous c-myc gene, but not of a viral Ha-ras gene, causes a 5- to 10-fold increase in the PKC-beta isoform transcript and protein. The insertion of ras into the exogenous myc-expressing 209 cells, in addition to causing phenotypic transition, results in the translocation of the PKC-beta protein from the cytosol to the membrane fraction and a decrease in membrane-associated PKC-alpha. Concomitant with these changes, the increased PKC isoform transcript levels induced by myc alone are completely reversed. These observations suggest that a complex set of PKC transcript and protein alterations, most prominently involving an increased PKC-beta protein level in the cell membrane, a decrease in PKC-alpha protein, and a decrease in all PKC isoform transcripts, may represent a fundamental event(s) for c-myc collaboration with Ha-ras to alter cell phenotype.
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PMID:c-myc gene-induced alterations in protein kinase C expression: a possible mechanism facilitating myc-ras gene complementation. 165 53

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell line, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype. v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we found erbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene like erbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.
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PMID:Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines. 169 Feb 10

Small cell lung cancer (SCLC) tumor progression can involve partial or complete conversion to a more treatment-resistant non-small cell (NSCLC) phenotype. In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene induced many NSCLC phenotypic features. We now report that the v-Ha-ras gene can also induce morphologic, biochemical, and growth characteristics consistent with the NSCLC phenotype in an N-myc amplified SCLC cell line, NCI-H249. We show that v-Ha-ras has novel effects on these cells, abrogating an SCLC-specific growth requirement for gastrin-releasing peptide, and inducing mRNA expression of three NSCLC-associated growth factors and receptors, platelet-derived growth factor B chain, transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). TGF-alpha secretion and EGF-R also appear, consistent with the induction of an autocrine loop previously shown to be growth stimulatory for NSCLC in culture. These data suggest that N-myc and v-Ha-ras represent functional classes of genes that may complement each other in bringing about the phenotypic alterations seen during SCLC tumor progression, and suggest that such alterations might include the appearance of growth factors and receptors of potential importance for the growth of the tumor and its surrounding stroma.
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PMID:v-rasH induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line. 216 28

We have examined the distribution of ras p21 oncoprotein expression in cytologic specimens from 73 primary bronchial carcinomas using an immunocytochemical analysis. The cytologic preparations studied represent the two major groups of histological types of lung cancer: Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC) (squamous cell carcinoma and adenocarcinoma). The differential expression of ras p21 oncoprotein correlated with histological classification and was found in 30% of 23 small cell lesions, 61% of 28 squamous cell lung carcinomas and 32% of 22 adenocarcinomas. The ras p21 oncoprotein was commonly expressed in NSCLC cases (48%) as compared to SCLC cases (30%).
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PMID:Immunocytochemical study of RAS oncoprotein in cytologic specimens of primary lung tumours. 216 47

With the development of molecular biological techniques the search for genetic alterations in cancer cells has resulted in the beginning of a molecular description of cellular transformation. Most of these genetic changes occur in genes which have a role in the control of cellular growth and development, the proto oncogenes. In the last decade, it has become clear that the myc and ras oncogene families are important in the carcinogenesis of human lung cancers. The myc oncogenes are usually found to be altered in small cell lung cancer (SCLC), and these alterations appear to correlate with rapid growth and progression. Mutations in the Kras gene are specific for adenocarcinoma, a subclass of non small cell lung cancer (NSCLC). Kras gene mutations are closely associated with tobacco smoking, since all were found in adenocarcinomas from patients with a history of smoking. The erbB oncogene, which encodes the epidermal growth factor receptor, is often highly expressed in epidermoid carcinomas. The roles for other oncogenes, such as raf or myb, as well as those of "suppressor" genes remain to be investigated, but may be of paramount importance. The study of alterations in proto oncogenes may aid in the (sub)classification and diagnosis of lung cancer, and may yield useful prognostic information in the near future.
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PMID:The molecular genetics of human lung cancer. 260 91

While the ability of the retroviral oncogene V-jun to transform chicken cells led to its discovery, the oncogenic potential of its cellular homologue, c-jun, which encodes a transcription factor, is unknown. We isolated a 1070-base-pair cDNA clone containing the unmutated entire open reading frame of c-jun from a human small cell lung cancer line. This cDNA as well as a 5.6-kilobase normal human genomic DNA fragment containing the c-jun gene were placed under the control of retroviral long terminal repeats and introduced into primary rat embryo cells (RECs), with or without other oncogenes, and into an immortal rat fibroblast cell line, Rat-1a, as a single gene. In Rat-1a cells the expression of human c-jun mRNA was associated with the ability to clone in soft agarose and form tumors in nude mice. When the c-jun cDNA or genomic DNA constructs were introduced into RECs, no foci of transformed cells were seen with c-jun alone or c-jun cotransfected with deregulated c-myc or L-myc protooncogenes. However, cotransfection of the c-jun constructs with an activated human c-Ha-ras gene led to foci of transformed cells which gave rise to immortalized cell lines that cloned in soft agarose and formed tumors in nude mice. Furthermore, formation of foci of transformed RECs by the c-jun/ras combination was augmented 3-fold by the tumor promoter phorbol 12-tetradecanoate 13-acetate. We conclude that deregulated expression of human c-jun can participate in malignant transformation of normal mammalian cells.
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PMID:Deregulated expression of human c-jun transforms primary rat embryo cells in cooperation with an activated c-Ha-ras gene and transforms rat-1a cells as a single gene. 264 96

Amplification and expression of 16 protooncogenes were examined in 12 established small cell lung cancer (SCLC) cell lines. Seven of 12 cell lines showed a 20- to 35-fold amplification of the c-myc oncogene, 3 cell lines showed an 80- to 130-fold amplification of N-myc oncogene, and one cell line had a simultaneous amplification of the c-myb and N-myc oncogene. In this cell line both oncogenes were transcriptionally highly active at the same time. A variant subpopulation of SCLC expressed an 8.5-kilobase v-fms homologous transcript at high levels but without amplification of the c-fms gene. All cell lines examined had similar RNA levels of the N-ras, Ki-ras, Ha-ras, and c-raf1 oncogenes. DNA amplification, however, was undetectable. The protooncogenes c-fes, c-fos, and c-erbB were expressed very weakly and the transcripts of the oncogenes c-mos, c-sis, c-erbA, c-src, and c-abl were not observed in any of the 12 SCLC-cell lines. From these data we conclude that beyond the oncogenes myc and myb, oncogenes whose gene products are GTP binding proteins and phosphokinases may also be necessary to develop and keep the malignant state of SCLC. The v-fms homologous transcript found may be involved in the transition of the classic cell type to the variant cell type of SCLC.
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PMID:Amplification and expression of protooncogenes in human small cell lung cancer cell lines. 282 28


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