Functional characterization of <it>Trip10 </it>in cancer cell growth and survival

• Main Authors: Yan Pearlly S, Chu Pei-Yi, Yeh Kun-Tu, Chen Chien-Min, Sun Wei-Sheng, Hung Yi-Chen, Lai Yen-Ling, Yen Jia-Yi, Kuo Tzen-Yu, Lee Kuan-Der, Tseng Min-Jen, Leu Yu-Wei, Hsu Chia-Chen, Chang Yu-Sun, Huang Tim H-M, Hsiao Shu-Huei
• Format: Article
• Language: English
• Published: BMC 2011-02-01
• Series: Journal of Biomedical Science
• Online Access: http://www.jbiomedsci.com/content/18/1/12

<p>Abstract</p> <p>Background</p> <p>The Cdc42-interacting protein-4, Trip10 (also known as CIP4), is a multi-domain adaptor protein involved in diverse cellular processes, which functions in a tissue-specific and cell lineage-specific manner. We previously found that <it>Trip10 </it>is highly expressed in estrogen receptor-expressing (ER⁺) breast cancer cells. Estrogen receptor depletion reduced <it>Trip10 </it>expression by progressively increasing DNA methylation. We hypothesized that <it>Trip10 </it>functions as a tumor suppressor and may be involved in the malignancy of ER-negative (ER^-) breast cancer. To test this hypothesis and evaluate whether <it>Trip10 </it>is epigenetically regulated by DNA methylation in other cancers, we evaluated DNA methylation of <it>Trip10 </it>in liver cancer, brain tumor, ovarian cancer, and breast cancer.</p> <p>Methods</p> <p>We applied methylation-specific polymerase chain reaction and bisulfite sequencing to determine the DNA methylation of <it>Trip10 </it>in various cancer cell lines and tumor specimens. We also overexpressed <it>Trip10 </it>to observe its effect on colony formation and <it>in vivo </it>tumorigenesis.</p> <p>Results</p> <p>We found that <it>Trip10 </it>is hypermethylated in brain tumor and breast cancer, but hypomethylated in liver cancer. Overexpressed <it>Trip10 </it>was associated with endogenous Cdc42 and huntingtin in IMR-32 brain tumor cells and CP70 ovarian cancer cells. However, overexpression of <it>Trip10 </it>promoted colony formation in IMR-32 cells and tumorigenesis in mice inoculated with IMR-32 cells, whereas overexpressed <it>Trip10 </it>substantially suppressed colony formation in CP70 cells and tumorigenesis in mice inoculated with CP70 cells.</p> <p>Conclusions</p> <p><it>Trip10 </it>regulates cancer cell growth and death in a cancer type-specific manner. Differential DNA methylation of <it>Trip10 </it>can either promote cell survival or cell death in a cell type-dependent manner.</p>