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Updated: Aug 3, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
Ovarian cancer cells that coexpress endogenous Rb and p16 are insensitive to overexpression of functional p16 protein
M C Todd1, R A Sclafani, T A Langan
1Department of Pharmacology, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, Colorado, CO 80262, USA.
Abstract:
Defects of the 'Rb/cyclin D1/p16 pathway' have been shown to play a critical role in the development of virtually all human malignancies assessed. To determine the contribution of G1 phase cell cycle defects to ovarian tumorigenesis, we have examined a panel of normal and tumor ovarian tissues and ovarian cancer cell lines for the expression of Rb, p16 and cyclin D1 proteins. Unlike most types of human cancer whose development involves the loss of either Rb or p16 expression, we observed the coexpression of Rb, p16 and cyclin D1 in 82% of ovarian cancer tissues and cell lines. Furthermore, the growth and cell cycle distribution profiles of three ovarian cancer cell lines (ES-2, PA-1 and NIH OVCAR-3) that coexpressed Rb and p16, were found to be unaffected by adenoviral-mediated overexpression of functional p16 protein, indicating the existence of a defect(s) downstream from p16 in these cells. By contrast overexpression of ectopic p16 in the one ovarian cancer cell line (SK-OV-3) that expressed Rb but lacked p16 protein, resulted in a G1 growth arrest. These data suggest that defects of the 'Rb/cyclin D1/p16 pathway', other than the loss of Rb or p16, may play a major role in the development of ovarian cancer.
Insights
Defects in the Rb/cyclin D1/p16 pathway are implicated in ovarian cancer. Ovarian cancers often coexpress Rb, p16, and cyclin D1, suggesting defects downstream of p16 contribute to tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Cell Cycle Regulation
Background:
- The Rb/cyclin D1/p16 pathway is crucial in preventing cell proliferation and is frequently disrupted in human cancers.
- Understanding cell cycle regulation defects is vital for identifying drivers of ovarian tumorigenesis.
Purpose of the Study:
- To investigate the role of G1 phase cell cycle defects in ovarian cancer development.
- To analyze the expression of Rb, p16, and cyclin D1 proteins in ovarian tissues and cell lines.
Main Methods:
- Western blot analysis to detect Rb, p16, and cyclin D1 protein expression in normal and tumor ovarian tissues and cell lines.
- Adenoviral-mediated gene delivery to overexpress functional p16 protein in ovarian cancer cell lines.
- Cell cycle analysis to assess the impact of p16 overexpression on cell growth and proliferation.
Main Results:
- Coexpression of Rb, p16, and cyclin D1 was observed in 82% of ovarian cancer tissues and cell lines.
- Overexpression of p16 did not affect cell cycle progression in ovarian cancer cell lines coexpressing Rb and p16.
- p16 reintroduction induced G1 growth arrest in an ovarian cancer cell line lacking p16 but expressing Rb.
Conclusions:
- The study suggests that defects in the Rb/cyclin D1/p16 pathway, beyond the loss of Rb or p16, are significant contributors to ovarian cancer.
- These findings highlight potential therapeutic targets downstream of p16 in ovarian tumorigenesis.
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