BRCA1 interacting protein COBRA1 facilitates adaptation to castrate-resistant growth conditions

Huiyoung Yun, Roble Bedolla, Aaron Horning, Rong Li, Huai Chin Chiang, Hui-ming Huang, Robert Reddick, Aria F. Olumi, Rita Ghosh, Addanki P Kumar

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2104
JournalInternational Journal of Molecular Sciences
Volume19
Issue number7
DOIs
StatePublished - Jul 1 2018

Fingerprint

BRCA1 Protein
Prostate
Cells
Cell proliferation
Androgen Receptors
proteins
Proteins
Prostatic Neoplasms
Androgens
Tumors
Growth
Cell Survival
Down-Regulation
Cell Proliferation
Gene expression
Animals
DNA Methylation
Genes
Transgenic Mice
Elongation

Keywords

  • Androgen receptor
  • COBRA1
  • CRPC
  • NELFB

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

BRCA1 interacting protein COBRA1 facilitates adaptation to castrate-resistant growth conditions. / Yun, Huiyoung; Bedolla, Roble; Horning, Aaron; Li, Rong; Chiang, Huai Chin; Huang, Hui-ming; Reddick, Robert; Olumi, Aria F.; Ghosh, Rita; Kumar, Addanki P.

In: International Journal of Molecular Sciences, Vol. 19, No. 7, 2104, 01.07.2018.

Research output: Contribution to journalArticle

Yun, Huiyoung ; Bedolla, Roble ; Horning, Aaron ; Li, Rong ; Chiang, Huai Chin ; Huang, Hui-ming ; Reddick, Robert ; Olumi, Aria F. ; Ghosh, Rita ; Kumar, Addanki P. / BRCA1 interacting protein COBRA1 facilitates adaptation to castrate-resistant growth conditions. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 7.
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