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 language | English (US) |
|---|---|
| Article number | 2104 |
| Journal | International Journal of Molecular Sciences |
| Volume | 19 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - BRCA1 interacting protein COBRA1 facilitates adaptation to castrate-resistant growth conditions
AU - Yun, Huiyoung
AU - Bedolla, Roble
AU - Horning, Aaron
AU - Li, Rong
AU - Chiang, Huai Chin
AU - Huang, Hui-ming
AU - Reddick, Robert
AU - Olumi, Aria F.
AU - Ghosh, Rita
AU - Kumar, Addanki P
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
KW - Androgen receptor
KW - COBRA1
KW - CRPC
KW - NELFB
UR - http://www.scopus.com/inward/record.url?scp=85050920985&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050920985&partnerID=8YFLogxK
U2 - 10.3390/ijms19072104
DO - 10.3390/ijms19072104
M3 - Article
C2 - 30036938
AN - SCOPUS:85050920985
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 7
M1 - 2104
ER -