- 作者: 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
- 作者服務機構: Human Epigenomics Center, Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: --