@article{c766889e26b94cefac962b0bcc956da0,
title = "BRCA1 interacting protein COBRA1 facilitates adaptation to castrate-resistant growth conditions",
abstract = "COBRA1 (co-factor of BRCA1) is one of the four subunits of the negative elongation factor originally identified as a BRCA1-interacting protein. Here, we provide first-time evidence for the oncogenic role of COBRA1 in prostate pathogenesis. COBRA1 is aberrantly expressed in prostate tumors. It positively influences androgen receptor (AR) target gene expression and promoter activity. Depletion of COBRA1 leads to decreased cell viability, proliferation, and anchorage-independent growth in prostate cancer cell lines. Conversely, over expression of COBRA1 significantly increases cell viability, proliferation, and anchorage-independent growth over the higher basal levels. Remarkably, AR-positive androgen dependent (LNCaP) cells over expressing COBRA1 survive under androgen-deprivation conditions. Remarkably, treatment of prostate cancer cells with well-studied antitumorigenic agent, 2-methoxyestradiol (2-ME2), caused significant DNA methylation changes in 3255 genes including COBRA1. Furthermore, treatment of prostate cancer cells with 2-ME2 down regulates COBRA1 and inhibition of prostate tumors in TRAMP (transgenic adenocarcinomas of mouse prostate) animals with 2-ME2 was also associated with decreased COBRA1 levels. These observations implicate a novel role for COBRA1 in progression to CRPC and suggest that COBRA1 down regulation has therapeutic potential.",
keywords = "Androgen receptor, COBRA1, CRPC, NELFB",
author = "Huiyoung Yun and Roble Bedolla and Aaron Horning and Rong Li and Chiang, {Huai Chin} and Huang, {Tim H.} and Robert Reddick and Olumi, {Aria F.} and Rita Ghosh and Kumar, {Addanki P.}",
note = "Funding Information: Funding: This research was supported in part by funds from Cancer Prevention Research Institute of Texas (CPRIT RP 150166) National Cancer Institute R01 CA135451; National Center for Complementary and Alternative Medicine AT 005513-01A1, AT007448-01; Veterans Affairs-Merit Award 1 I01 BX 000766-01 & BX 003876 (APK); R01 CA149516 (RG); R01 CA220578 (RL) and a postdoctoral fellowship to H-C. C from NIH (T32CA148724). APK acknowledge support provided by the CTRC 40th Anniversary Distinguished Professor of Oncology Endowment. We acknowledge support provided by Bioanalytics and Single-Cell Core (BASiC) core facility at UT Health San Antonio and UT Health San Antonio Cancer Center through the National Cancer Institute support grant #2P30 CA 054174-17 (APK and RG). Funding Information: This research was supported in part by funds from Cancer Prevention Research Institute of Texas (CPRIT RP 150166) National Cancer Institute NCIR01 CA135451; National Center for Complementary and Alternative Medicine NCCAM AT005513-01A1, National Center for Complementary and Alternative MedicineNCCAMAT007448-01; Veterans Affairs-Merit Award 1 I01 BX 000766-01 & BX 003876 (APK); R01 CA149516 (RG); R01 CA220578 (RL) and a postdoctoral fellowship to H-C. C from NIH National Institutes of Health (T32CA148724). APK acknowledge support provided by the CTRC 40th Anniversary Distinguished Professor of Oncology Endowment. We acknowledge support provided by Bioanalytics and Single-Cell Core (BASiC) core facility at UT Health San Antonio and UT Health San Antonio Cancer Center through the National Cancer Institute NCI support grant #2P30 CA 054174-17 (APK and RG). Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2018",
month = jul,
doi = "10.3390/ijms19072104",
language = "English (US)",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",
}