Mutation and expression of the p27KIP1 and p57KIP2 genes in human gastric cancer

Abstract

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.

The cell cycle inhibitor p57Kip2 promotes cell death via the mitochondrial apoptotic pathway

“…7 Taken together, these observations suggest that that p57 Kip2 exerts tissue-specific effects during development. Interestingly during adulthood, it has also been reported that p57 Kip2 expression is reduced in various tumors, [8][9][10][11][12][20][21][22][23][24] suggesting a possible function for this protein in tumorigenesis. Importantly, decreased p57 Kip2 expression may provide an important prognostic implication for patients with ovarian, hepatocellular and colorectal cancers, and acute lymphoblastic leukemia.…”

“…[8][9][10]23 In spite of frequent low/absence of p57 Kip2 expression in various tumors, rare/no somatic mutations of p57 Kip2 gene are found in these tumors. [8][9][10][11][12] These observations suggest that inactivation of p57 Kip2 gene expression, rather than mutations in the p57 Kip2 gene, accounts for the involvement of p57 Kip2 in other types of cancer. Accordingly, inactivation of p57 Kip2 by regional promoter hypermethylation and histone deacetylation has been suggested in human tumors.…”

“…Importantly, the p57 Kip2 gene, located on chromosome 11p15.5, has been suggested to be a tumor suppressor gene, being inactivated in various types of human cancers. [8][9][10][11][12] However, little is known concerning p57 Kip2 function during apoptotic cell death during adulthood and its possible implication for cancer.…”

p57Kip2 and Cancer: Time for a Critical Appraisal

“…In a study by Shin and colleagues in 2000 (125), neither mutations of the CDKN1C gene (30 samples) nor its reduced expression in gastric cancer cell lines were reported. Conversely, p57 Kip2 immunoblotting analysis in gastric cancer specimens showed lower levels of the protein (in 36 patients) compared with normal counterparts (126).…”

Effect of Trichostatin A on CNE2 Nasopharyngeal Carcinoma Cells - Genome-wide DNA Methylation Alteration

“…Histone acetylation status is regulated by the opposing actions of histone acetyl-transferases (HATs) and histone deacetylases (HDACs) (Smith and Denu, 2009). During the last years HDAC-inhibitors have become one of the most promising classes of chemotherapeutics with profound antitumour effects (Glaser, 2007), and are successfully used to inhibit cell growth of lots of carcinoma cells in vitro (McBain et al, 1997;Shin et al, 2000).…”