Role of Cell Cycle Regulators in Multistage Carcinogenesis of Human Oral Keratinocytes = 사람 구강각화세포의 다단계 발암과정에서 세포주기 조절인자들의 활성 및 발현 변화에 관한 연구

다국어 초록 (Multilingual Abstract)

Cyclin-cdk complexes are subject to a careful control through signaling transduction pathways and feedback loops which ensure that each event is performed correctly and in proper sequence. Perturbations of some of these regulatory proteins may play a role in cancer. To investigate the role of cell cycle regulators in multistage carcinogenesis of human oral keratinocytes, we correlated multistage carcinogenesis with the cellular levels or activities of key G₁phase cell cycle regulatory proteins in normal, HPV-immortalized and two tumor cell lines derived from HPV-immortalized oral keratinocytes. There was a significant decrease in the expression of p21^WAF1/CIP1 during malignant conversion of the normal cells, and the down-regulation of p21^WAF1/CIP1 expression was associated with cell cycle regulators resulting in an increase in the levels of cyclin E, cdk2 and cdk4. The level of p21^WAF1/CIP1 protein was notably increased after TGF-β_1 treatment in these cells. The p21^WAF1/CIP1 protein level showed a notably increase in NHOK after calcium treatment. These results support that unlike normal cells, the HPV-immortalized oral keratinocytes could readily convert to neoplastic cells because of their capability to stimulate cell cycle and perform DNA repair inefficiently when challenged with genotoxic agents. It is also support that loss of the responsiveness to growth inhibitory factors in the tumorigenic cells could be associated with their inability for induction of p21^WAF1/CIP1 protein.

목차 (Table of Contents)

• INTRODUCTION
• MATERIALS AND METHODS
• RESULTS
• DISCUSSION
• CONCLUSION
• REFERENCES
• ABSTRACT