Expression of cyclin D1, PCNA, RB and p16 associated with G1 cell-cycle in DMBA induced rat ovarian carcinogenesis

Hwang, Sun Bo; Lee, Dong Gi; Heo, Hyeok; Kim, Do Gyun; Kim, Jong Ho; Yang, Hoe Saeng; Yoon, Hae Won; Sim, Jae Chul; Kim, Ki Kweon; Kim, Jung Ran

Abstract

OBJECTIVE
Ovarian cancer is common a gynecologic malignancy and leading cause of death in women being diagnosed with advanced disease. This study was undertaken to investigate the roles of the proteins related to G1 cell cycle in ovarian carcinogenesis.
METHODS
The expression of cyclin Dl, p16, RB and PCNA in DMBA (7, 12-dimethylbenzanthracene)-induced ovarian cancer of rats was analyzed by immuno-histochemistry and Western blot.
RESULTS
1. Twenty-nine tumors were induced in 32 ovaries from 16 rats (90.6%) in the experimental group. The average weight of tumor was 3.35+/-0.73 gm and the average size was 1.84+/-0.17 cm in greatest dimension. The histologic types were adenocarcinomas (n=20), squamous cell carcinomas (n=3), sarcoma (n=4) and combined types (n=3). 2. With respect to the cyclin D1 and PCNA labelling index, ovarian cancers showed significantly higher index than normal ovarian surface epithelium. There were no differences among the cancer types. In Western blot analysis, the expression of cyclin Dl in ovarian cancers was higher than that in normal ovarian surface epithelium. 3. With respect to the p16 and RB labelling index, ovarian cancers showed significantly lower index than normal ovarian surface epithelium. There were no differences among the cancer types. In Western blot analysis, the expression of cyclin Dl in ovarian cancers were lower than that in normal ovarian surface epithelium. 4. Positive correlation was shown among cyclin D1, PCNA. RB was negatively correlated with cyclin D1, PCNA. The p16 had no correlation with cyclin D1, PCNA.
CONCLUSION
These results suggest that the deregulation of cyclin Dl, p16, RB and PCNA occur in DMBA induced rat ovarian carcinogenesis and result in tumor progression. Further studies are needed to investigate the role and function of cyclin Dl-p16-RB pathway in human ovarian cancer with this animal model.