BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions

التفاصيل البيبلوغرافية
العنوان: BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions
المؤلفون: Rita Ghosh, Aria F. Olumi, Rong Li, Addanki P. Kumar, Robert Reddick, Huiyoung Yun, Tim-H Huang, Huai-Chin Chiang, Aaron Horning, Roble Bedolla
المصدر: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 19, Iss 7, p 2104 (2018)
Volume 19
Issue 7
سنة النشر: 2018
مصطلحات موضوعية: 0301 basic medicine, Male, lcsh:Chemistry, Prostate cancer, Mice, NELFB, 0302 clinical medicine, Prostate, androgen receptor, CRPC, lcsh:QH301-705.5, Spectroscopy, Estradiol, BRCA1 Protein, Nuclear Proteins, RNA-Binding Proteins, General Medicine, 3. Good health, Computer Science Applications, Gene Expression Regulation, Neoplastic, COBRA1, medicine.anatomical_structure, Receptors, Androgen, 030220 oncology & carcinogenesis, DNA methylation, Tramp, Protein Binding, Cell Survival, Biology, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Downregulation and upregulation, LNCaP, medicine, Animals, Humans, Viability assay, Physical and Theoretical Chemistry, Molecular Biology, Cell Proliferation, Organic Chemistry, Prostatic Neoplasms, DNA Methylation, medicine.disease, 2-Methoxyestradiol, Androgen receptor, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Cancer research, Transcription Factors
الوصف: 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, overexpression of COBRA1 significantly increases cell viability, proliferation, and anchorage-independent growth over the higher basal levels. Remarkably, AR-positive androgen dependent (LNCaP) cells overexpressing 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 downregulates 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 downregulation has therapeutic potential.
وصف الملف: application/pdf
تدمد: 1422-0067
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2b922a7703289e2205d144aefc684f0
https://pubmed.ncbi.nlm.nih.gov/30036938
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....b2b922a7703289e2205d144aefc684f0
قاعدة البيانات: OpenAIRE