Abstract
Abstract CDC25B is a dual specificity phosphatase that activates cyclin-dependent kinases to trigger entry into mitosis and is required for re-entry into mitosis after DNA damage. As an oncogene, CDC25B is overexpressed in multiple tumor types. It has been specifically associated with prostate cancer, where overexpression is seen in prostate tumor tissues and higher levels correlate with increased tumor grade. In the prostate, in addition to its role as a cell cycle regulator, CDC25B acts as an androgen receptor coactivator increasing the response of reporter genes to the addition of androgen analogues. In a transgenic mouse model, overexpression of CDC25B in the mammary glands led to accelerated mammary epithelial proliferation resulting in hyperplasia, while in vitro, co-transfection of CDC25B with Ras allows for transformation of MEF's. Surprisingly, given the establishment of CDC25B as an oncogene, colony formation assays using ectopic expression of CDC25B in transformed cell lines reveal an anti-proliferative effect. Our data reveal a role for Ras inhibition as a cause of this anti-proliferative effect. Co-transfection of CDC25B and Ras results in a dose-dependent decrease in expression of the ectopic Ras protein in several cell lines tested. Preliminary experiments suggest that while mRNA levels remain stable, CDC25B inhibits Ras protein expression. As Ras is pivotal in multiple tumors, this effect of CDC25B may be broadly applicable. These data therefore reveal a new role for CDC25B, which may need to be overcome to allow transformation of tumor cells. Citation Format: Caleb C. Lee, James Manfredi. Investigating the role of CDC25B in inhibition of cellular proliferation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5094. doi:10.1158/1538-7445.AM2014-5094
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