Relation between the Low Molecular Weight Cyclin E and Mutator Phenotype in Sporadic Colorectal Cancer

Park, Dong Guk

Abstract

PURPOSE
Cyclin E/CDK2 complexes are thought to play critical roles in multiple cell cycle events, including DNA replication, centrosome duplication, and activation of the E2F transcriptional program. Deregulation of the cell cycle control mechanism is an obligatory step in tumorigenesis. Cyclin E gene amplification and the high expression of low molecular weight (LMW) cyclin E proteins are reported to be important events in breast, and other cancers. According to recent studies, the overexpression of cyclin E protein has the role of developing chromosomal and microsatellite instability (MSI). MSI is known as one of the pathways by which colorectal cancer develops. LMW cyclin E variants are also expressed exclusively in cancer tissues. Therefore, we hypothesize that the LMW cyclin E maybe related to the MSI in sporadic colorectal cancers. METHODS: The expressions of the LMW cyclin E, CDK2 proteins and MSI stati were detected by western blot and PCR-SSCP analysis, respectively, using five Bethesda microsatellite markers in 49 sporadic colorectal cancers, which were compared with matched normal colonic mucosal tissues. RESULTS: There were 5, 10 and 34 cases of MSI-H (10.2%), MSI-L (20.4%) and MSS (69.4%), respectively. LMW cyclin E was over-expressed in 4 of the 5 MSI-H (80%) and 31 of the 44 MSI-L and MSS cases (70.5%). No correlation was found between LMW cyclin E (Fisher exact one-tailed P= 0.554), CDK2 expression (Fisher exact one-tailed P=0.569) and microsatellite instability in sporadic colorectal cancers. CONCLUSION: The expression of the LMW cyclin E variant was not associated with the MSI status in sporadic colorectal cancers.