자궁경부암 세포주에서 세포주기조절 유전자들의 발현

Abstract

Purpose: Recently, many aspects of biological functions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors and Rb gene have been reported, and the ceil cycle control genes are considered to act important roles in tumorigenesis. In this study, the expression patterns of major cell cycle control genes (cyclin A, B, C, Dl, E, E2F, pl6rNK4a, p21WAF1 and Rb) in various human cervical cancer cells were analysed to elucidate the impacts of the cell cycle control genes on the carcinogenesis of human cervical cancer. Materials and Methods: The expression patterns of major cell cycle control genes in HT-3, C33-A, HeLa, C4-II, SiHa and CaSki human uterine cervical cancer cells were analysed by using western blot and reverse transcription-polymerase chain reaction (RT-PCR). Results: In most of the cervical cancer cells tested, the overexpressions of cyclin A, E, E2F and markedly decreased expression of Rb tumor suppressor proteins were observed. By comparing RNA and protein expressions in each cancer cells, the mechanisms of increased expressions of cyclin A, E and decreased expression of Rb were elucidated as post-translational controls. Conclusion: The cervical carcinogenesis caused by the altered expressions of the major cell cycle control genes can be hypothesized as follows: overexpressions of cyclin E and A cause acceleration of Rb phosphorylations and E2F overexpression; increased E2F function accelerates Gl/S transition of the cells; compensatory increase of pl6INK4a cannot stop the cells in G1 phase because Rb expression is severely decreased; consequently, loss of Rb function, G1 shortening, inappropriate cell division and decreased function of the maintenance of genomic stability occur. In addition to these alterations, loss of functions further accelerate instability of genome and decrease the susceptability to cell death. Furthermore, overexpression of Bcl2 protects these abnormal cells from apoptosis. All these derangements of cell cycle control should contribute to the human cervical carcinogenesis.