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Functional characterization of Trip10 in cancer cell growth and survival.

Hsu CC, Leu YW, Tseng MJ, Lee KD, Kuo TY, Yen JY, Lai YL, Hung YC, Sun WS, Chen CM, Chu PY, Yeh KT, Yan PS, Chang YS, Huang TH, Hsiao SH - J. Biomed. Sci. (2011)

Bottom Line: 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 found that Trip10 is hypermethylated in brain tumor and breast cancer, but hypomethylated in liver cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Human Epigenomics Center, Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan.

ABSTRACT

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.

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Differential methylation of Trip10 in breast and liver cancers. Representative DNA methylation of (A) breast cancer tissue and (B) liver cancer compared with adjacent non-tumor tissues. Results are expressed as mean and standard deviation. Breast cancer, n = 93 pairs; liver cancer, n = 36 pairs. *Analyzed by paired Student t-test.
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Figure 2: Differential methylation of Trip10 in breast and liver cancers. Representative DNA methylation of (A) breast cancer tissue and (B) liver cancer compared with adjacent non-tumor tissues. Results are expressed as mean and standard deviation. Breast cancer, n = 93 pairs; liver cancer, n = 36 pairs. *Analyzed by paired Student t-test.

Mentions: To determine Trip10 methylation in vivo, we examined Trip10 promoter methylation in human breast cancer and liver cancer specimens and adjacent non-tumor tissues. As illustrated in Figure 2Trip10 was hypermethylated in breast cancer (Figure 2A), but hypomethylated in liver cancer (Figure 2B). Together, these data demonstrate that Trip10 is subject to epigenetic modification by DNA methylation in breast cancer and liver cancer tumorigenesis. Aberrant DNA methylation of Trip10 occurs in vivo and may contribute to neoplasm development.


Functional characterization of Trip10 in cancer cell growth and survival.

Hsu CC, Leu YW, Tseng MJ, Lee KD, Kuo TY, Yen JY, Lai YL, Hung YC, Sun WS, Chen CM, Chu PY, Yeh KT, Yan PS, Chang YS, Huang TH, Hsiao SH - J. Biomed. Sci. (2011)

Differential methylation of Trip10 in breast and liver cancers. Representative DNA methylation of (A) breast cancer tissue and (B) liver cancer compared with adjacent non-tumor tissues. Results are expressed as mean and standard deviation. Breast cancer, n = 93 pairs; liver cancer, n = 36 pairs. *Analyzed by paired Student t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3044094&req=5

Figure 2: Differential methylation of Trip10 in breast and liver cancers. Representative DNA methylation of (A) breast cancer tissue and (B) liver cancer compared with adjacent non-tumor tissues. Results are expressed as mean and standard deviation. Breast cancer, n = 93 pairs; liver cancer, n = 36 pairs. *Analyzed by paired Student t-test.
Mentions: To determine Trip10 methylation in vivo, we examined Trip10 promoter methylation in human breast cancer and liver cancer specimens and adjacent non-tumor tissues. As illustrated in Figure 2Trip10 was hypermethylated in breast cancer (Figure 2A), but hypomethylated in liver cancer (Figure 2B). Together, these data demonstrate that Trip10 is subject to epigenetic modification by DNA methylation in breast cancer and liver cancer tumorigenesis. Aberrant DNA methylation of Trip10 occurs in vivo and may contribute to neoplasm development.

Bottom Line: 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 found that Trip10 is hypermethylated in brain tumor and breast cancer, but hypomethylated in liver cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Human Epigenomics Center, Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus