Functional characterization of Trip10 in cancer cell growth and survival

Journal of Biomedical Science

Research

Kuan-Der Lee¹  Kun-Tu Yeh²  Pei-Yi Chu²  Pearlly S Yan³  Tim H-M Huang³  Chien-Min Chen⁴  Yu-Sun Chang⁵  Tzen-Yu Kuo⁶  Yu-Wei Leu⁶  Wei-Sheng Sun⁶  Shu-Huei Hsiao⁶  Min-Jen Tseng⁶  Chia-Chen Hsu⁶  Yi-Chen Hung⁶  Yen-Ling Lai⁶  Jia-Yi Yen⁶ 

[1] Chang Gung Memorial Hospital, Chia-Yi, Taiwan;Department of Pathology, ChangHua Christian Hospital, ChangHua, Taiwan;Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics, and the Comprehensive Cancer Center, The Ohio State University, 43210, Columbus, OH, USA;Division of Neurosurgery, ChangHua Christian Hospital, ChangHua, Taiwan;Graduate Institute of Basic Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan;Human Epigenomics Center, Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan;

关键词: Colony Formation;    Bisulfite Sequencing;    Brain Tumor Cell;    Akt3 Expression;    CP70 Cell;   

DOI  :  10.1186/1423-0127-18-12

 received in 2010-09-26, accepted in 2011-02-07,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsTrip10 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.

【 授权许可】

Unknown   
© Hsu et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.