Genetic status and expression of the cyclin-dependent kinase inhibitors in human gastric carcinoma cell lines.
Deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a pivotal role in the development of diverse human cancers. We examined the genetic status and the expression of CDK inhibitors (p21, p27, p16 and p15), CDK2 and cyclins (A, D1 and E) in eight gastric carcinoma cell lines, in comparison with the status of p53 gene alterations. All the cell lines (except MKN-28) that contained a p53 gene abnormality expressed very low or undetectable levels of p21 mRNA, while the cell lines (MKN-45 and -74) with wild-type p53 gene expressed high levels of p21 mRNA. An inverse correlation was found between the level of p21 mRNA and the expression of mRNAs for CDK2 and G1 cyclins. MKN-28 was an exception; it contained mutated p53, and expressed mRNAs for p21, CDK2 and G1 cyclins at high levels. Only MKN-45 and -74, with wild-type p53, expressed considerable levels of p21 protein. Homozygous deletion of the p16 and p15 genes was detected in two (MKN-45 and HSC-39) of the eight gastric carcinoma cell lines, p16 protein was not expressed in three cell lines (MKN-28, MKN-74 and KATO-III), as well as MKN-45 and HSC-39. Rearrangement of the p15 gene was found in TMK-1. Rearrangement of the p27 gene was detected in MKN-45, although the expression of p27 protein was well preserved in all the gastric carcinoma cell lines. The expression of pRb was also preserved in all the cell lines except KATO-III. No obvious correlation was observed between the p53 gene status and the expression of p27 and p16. These findings suggest that abnormal regulation of CDK2/cyclins and CDK inhibitors might be involved in deregulated growth of gastric carcinomas.
Akama
Y
Y
Department of Oral and Maxillofacial Surgery II, Hiroshima University School of Dentistry.
Yasui
W
W
Kuniyasu
H
H
Yokozaki
H
H
Akagi
M
M
Tahara
H
H
Ishikawa
T
T
Tahara
E
E
D000230:Adenocarcinoma / Q000235:genetics; D042846:CDC2-CDC28 Kinases; D018196:Carcinoma, Adenosquamous / Q000235:genetics; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D015342:DNA Probes; D004791:Enzyme Inhibitors; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D015342:DNA Probes; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases