Mutation and expression of the p27KIP1 and p57KIP2 genes in human gastric cancer.
Cyclin-dependent kinase inhibitors (CDKI) are negative regulators of cell cycle progression by binding the cyclin-CDK complex and inhibiting the CDK activity. Genetic alteration in the CDKI genes has been implicated for carcinogenesis. To test the genetic alteration in the p27 and p57 genes, KIP family CDKI genes, 30 gastric tumor-normal pairs and 8 gastric cancer cell lines were analyzed for mutations by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). No mutation was detected in these genes although length polymorphisms in the proline-alanine repeat of the p57 gene were detected. When the p27 and p57 mRNAs were analyzed in gastric cancer cell lines by RT-PCR, the p27 mRNA was expressed considerably high in tumor cells but expression of the p57 mRNA was much low in gastric cancer cell lines compared to that of normal cells. The result suggests that inactivation of gene expression rather than mutations in the p57 gene accounts possibly for the involvement of this gene in tumorigenesis of gastric cancer. However, expression of the p27 gene seems to be essential for cell survival.
Department of Biochemistry, College of Medicine, Hallym University, Chunchon, Kangwon-do, Korea.
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Shin
H S
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Kim
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Lee
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Kim
J B
JB
Park
M H
MH
Won
S W
SW
Chae
Y H
YH
Choi
K C
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Choi
Y E
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Park
J Y
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Lee
D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004791:Enzyme Inhibitors; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493964:CDKN1C protein, human; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases