Functional characterization of Trip10 in cancer cell growth and survival

Chia Chen Hsu, Yu Wei Leu, Min Jen Tseng, Kuan Der Lee, Tzen Yu Kuo, Jia Yi Yen, Yen Ling Lai, Yi Chen Hung, Wei Sheng Sun, Chien Min Chen, Pei Yi Chu, Kun Tu Yeh, Pearlly S. Yan, Yu Sun Chang, Tim H.M. Huang, Shu Huei Hsiao

研究成果: 雜誌貢獻文章

16 引文 斯高帕斯(Scopus)

摘要

Background. 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 Trip10 is highly expressed in estrogen receptor-expressing (ER +) breast cancer cells. Estrogen receptor depletion reduced Trip10 expression by progressively increasing DNA methylation. We hypothesized that Trip10 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 Trip10 is epigenetically regulated by DNA methylation in other cancers, we evaluated DNA methylation of Trip10 in liver cancer, brain tumor, ovarian cancer, and breast cancer. Methods. We applied methylation-specific polymerase chain reaction and bisulfite sequencing to determine the DNA methylation of Trip10 in various cancer cell lines and tumor specimens. We also overexpressed Trip10 to observe its effect on colony formation and in vivo tumorigenesis. Results. We found that Trip10 is hypermethylated in brain tumor and breast cancer, but hypomethylated in liver cancer. Overexpressed Trip10 was associated with endogenous Cdc42 and huntingtin in IMR-32 brain tumor cells and CP70 ovarian cancer cells. However, overexpression of Trip10 promoted colony formation in IMR-32 cells and tumorigenesis in mice inoculated with IMR-32 cells, whereas overexpressed Trip10 substantially suppressed colony formation in CP70 cells and tumorigenesis in mice inoculated with CP70 cells. Conclusions. Trip10 regulates cancer cell growth and death in a cancer type-specific manner. Differential DNA methylation of Trip10 can either promote cell survival or cell death in a cell type-dependent manner.
原文英語
文章編號12
期刊Journal of Biomedical Science
18
發行號1
DOIs
出版狀態已發佈 - 2011
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

引用此

Hsu, C. C., Leu, Y. W., Tseng, M. J., Lee, K. D., Kuo, T. Y., Yen, J. Y., Lai, Y. L., Hung, Y. C., Sun, W. S., Chen, C. M., Chu, P. Y., Yeh, K. T., Yan, P. S., Chang, Y. S., Huang, T. H. M., & Hsiao, S. H. (2011). Functional characterization of Trip10 in cancer cell growth and survival. Journal of Biomedical Science, 18(1), [12]. https://doi.org/10.1186/1423-0127-18-12