Differential expression of proteins related to START checkpoint of the cell cycle in human stomach, lung, cervix and liver cancers

Abstract

START (restriction) checkpoint in late G1 of the cell cycle is important in the regulation of cell proliferation. Many tumors have shown abnormalities partly in the components such as p53, proliferating cell nuclear antigen (PCNA), retinoblastoma protein (pRb), cyclin dependent kinase 4 (CDK4), cyclin D1 and cyclin dependent kinase inhibitors (CDIs) were involved in the START checkpoint. To determine the differential expression of p53, PCNA, CDK4 and pRb in most common human cancers in Korea, immunohistochemical analyses for these proteins were performed on each 20 formalin-fixed and paraffin-embedded tumor tissues of stomach adenocarcinomas, lung cancers, cervix cancers and liver cancers. Significant differences existed in the expression of the proteins among the cancers from different anatomic sites, Stomach adenocarcinomas (55%) and small cell lung cancers (SCLCs) (70%) had high rate of p53 overexpression, Overexpression of pRb was shown in 70% of stomach adenocarcinomas and 90% non small cell lung cancers (NSCLSs). SCLCs had the highest rate (80%) of pRb negativities, Cervix cancers showed the highest rate (60%) of CDK4 overexpression and lower rate (15%) of p53 overexpression. Liver cancers had the highest rate (90%) of PCNA overexpression and the lowest rate (10%) of p53 overexpression. Our results indicate that, at least, one of the abnormalities in p53, PCNA, CDK4 or pRb function occurs very commonly in these cancers, thereby, suggesting that components in restriction checkpoint play a critical role in the development of these cancers through functional inactivation of pRb.