Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Point mutations and deletions in the p53 tumor suppressor gene occur frequently in advanced stage bladder tumors. To extend these observations to an in vitro model of bladder tumorigenicity, we have evaluated the presence of p53 mutations in a panel of bladder carcinoma cell lines. p53 alleles were cloned using the reverse transcriptase-polymerase chain reaction method, and exons 2-11 were sequenced. Of 11 cell lines examined, 5 cell lines had missense point mutations, and each overexpressed p53 protein on western blot analysis. Except for the HT-1197 cell line, these point mutations occurred in evolutionarily conserved domains, which are characteristic hot spots for mutations. HT-1197 encodes an unusual C-terminal point mutation in codon 365, within the basic motif tetramerization domain, suggesting a linkage between induction of a mutant p53 conformation and alterations in protein oligomerization. Six of 11 cell lines had wild-type levels of p53 expression, with 4 producing p53 proteins having either internal deletions or truncations, and 2 producing wild-type p53. Presence of wild-type p53 was found only in cell lines derived from either a low-grade, papillary tumor (RT4) or fetal bladder (FHs 738Bl). The T24 cell line was found to contain a novel p53 mutant having an in-frame deletion of tyrosine 126. This p53 mutant does not bind SV40 large T antigen, yet is expressed at low levels, comparable to cell lines containing wild-type p53 alleles. Our findings characterize p53 mutations in a panel of bladder carcinoma cell lines, and provide a model for testing the role of wild-type or mutant p53 cDNA to suppress or induce tumorigenic properties.
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PMID:p53 mutations in bladder carcinoma cell lines. 778 50

A decrease in the intracellular concentrations of the transcripts for some tumor suppressor genes has been found during murine lung tumorigenesis; for p15INK4b and p16INK4a, this was due to homozygous deletions. We report here a decrease in the mRNA levels of the mutated in colorectal cancer (Mcc) and adenomatous polyposis coli (Apc) genes in mouse lung tumors and some neoplastic cell lines. This was assessed both by northern blotting and reverse transcriptase-polymerase chain reaction of RNA isolated from lung tumors that had been induced by urethane, N-nitrosodiethylamine, or 3-methylcholanthrene in (A/J x C57BL/6) F1 or A/J mice. A reduced amount of both Mcc and Apc messages was also seen when two neoplastic cell lines, a spontaneous transformant (E9) and a line derived from a chemically induced solid tumor (82-132), were compared with two independently derived nontumorigenic cell lines (E10 and C10); E9 was derived from E10, and all of these lines are probably of alveolar type 2 cell origin. A cell line derived from a chemically induced papillary lung tumor probably of bronchiolar Clara cell origin (LM2) had Mcc mRNA levels similar to those of C10 and E10 but reduced Apc mRNA levels. A line (p53-823) derived from a papillary tumor that arose in a mouse with a mutated p53 transgene had a reduced amount of the Mcc gene product only. These differential changes in the relative amounts of Apc and Mcc messages in LM2 and p53-823) cells may serve as useful models for studying the regulation of their expression. Both messages had half-lives of 6-9 h in normal E10 and neoplastic E9 cells, so decreased message stability does not account for these reductions. This is the first report of estimated degradation rates of these mRNAs. Apc and Mcc message content did not vary as a function of growth status of the cell lines. Single-strand conformation polymorphism analysis did not reveal mutations in Apc coding regions known to have a high mutation frequency in human colon tumors. Loss of heterozygosity of Apc and Mcc was not found in tumors that developed in the F1 mice, implying a lack of allelic deletions. These changes in tumor suppressor gene expression may contribute to the development and maintenance of neoplasia in lung epithelium.
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PMID:Decreased expression of the adenomatous polyposis coli (Apc) and mutated in colorectal cancer (Mcc) genes in mouse lung neoplasia. 947 70