Role of transcriptional corepressor CtBP1 in prostate cancer progression.

Abstract

Transcriptional repressors and corepressors play a critical role in cellular homeostasis and are frequently altered in cancer. C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a role in multiple cancers. In this study, we observed the overexpression and mislocalization of CtBP1 in metastatic prostate cancer and demonstrated the functional significance of CtBP1 in prostate cancer progression. Transient and stable knockdown of CtBP1 in prostate cancer cells inhibited their proliferation and invasion. Expression profiling studies of prostate cancer cell lines revealed that multiple tumor suppressor genes are repressed by CtBP1. Furthermore, our studies indicate a role for CtBP1 in conferring radiation resistance to prostate cancer cell lines. In vivo studies using chicken chorioallantoic membrane assay, xenograft studies, and murine metastasis models suggested a role for CtBP1 in prostate tumor growth and metastasis. Taken together, our studies demonstrated that dysregulated expression of CtBP1 plays an important role in prostate cancer progression and may serve as a viable therapeutic target.

• Authors: Rui Wang, Irfan A Asangani, Balabhadrapatruni V S K Chakravarthi, Bushra Ateeq, Robert J Lonigro, Qi Cao, Ram-Shankar Mani, Daniel F Camacho, Natalie McGregor, Taibriana E W Schumann, Xiaojun Jing, Radhika Menawat, Scott A Tomlins, Heng Zheng, Arie P Otte, Rohit Mehra, Javed Siddiqui, Saravana M Dhanasekaran, Mukesh K Nyati, Kenneth J Pienta, Nallasivam Palanisamy, Lakshmi P Kunju, Mark A Rubin, Arul M Chinnaiyan, Sooryanarayana Varambally
• Journal: Neoplasia (New York, N.Y.) (Neoplasia) Vol. 14 Issue 10 Pg. 905-14 (Oct 2012) ISSN: 1476-5586 [Electronic] United States
• PMID: 23097625 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• DNA-Binding Proteins
• RNA, Small Interfering
• Alcohol Oxidoreductases
• C-terminal binding protein

Topics

• Alcohol Oxidoreductases (antagonists & inhibitors, genetics, metabolism)
• Animals
• Apoptosis
• Blotting, Western
• Cell Movement
• Cell Proliferation
• Chick Embryo
• Chorioallantoic Membrane (metabolism, pathology)
• Chromatin Immunoprecipitation
• DNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• Gene Expression Profiling
• Genes, Tumor Suppressor
• Humans
• Immunoenzyme Techniques
• Lung Neoplasms (genetics, prevention & control, secondary)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Prostatic Neoplasms (genetics, pathology, prevention & control)
• RNA, Small Interfering (genetics)
• Radiation Tolerance
• Tumor Cells, Cultured