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

We have examined post-translational modification of the L-myc protein using polyclonal and monoclonal antibodies against a peptide well conserved in the predicted amino acid sequences of the c-myc, N-myc and L-myc genes. These antibodies precipitate three polypeptides of Mr 60-66,000 from [35S]methionine or [32P]orthophosphate-labelled human small cell lung cancer cell lines expressing amplified L-myc genes, but not the other myc genes. Treatment of the L-myc immunoprecipitates with alkaline phosphatase prior to electrophoresis converts the three methionine-labelled polypeptides into a single band migrating at Mr 59,000, and efficiently removes radioactivity from the 32P-labelled L-myc protein, suggesting that, in contrast to the c-myc and N-myc proteins, the L-myc polypeptide heterogeneity is due to differential phosphorylation of a common precursor. When the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or serum is added to cultures of U-1690 cells the Mr 66,000 polypeptide is rapidly enriched while the Mr 60,000 form is decreased in the L-myc immunoprecipitates. This effect is correlated with the ability of phorbol ester and diacylglycerol analogues to activate protein kinase C. The TPA-induced phosphorylation of the L-myc protein occurs in a protein synthesis-independent manner as it is not inhibited by cycloheximide or anisomycin. These data indicate that the phosphorylation of the L-myc nuclear oncoprotein is modulated in response to TPA via a rapid signal transduction system involving protein kinase C. This mechanism could play an important role in the response of lung cells to e.g. bombesin-related growth factors.
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PMID:Rapid phosphorylation of the L-myc protein induced by phorbol ester tumor promoters and serum. 254 Sep 55