Effect of TPA and HTLV-1 Tax on BRCA1 and ERE controlled genes expression

Autor: Ammar Abou-Kandil, Aya Abu-Jaafar, Mahmoud Huleihel, Azhar Jabareen
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Transcription
Genetic
Biology
Response Elements
law.invention
03 medical and health sciences
Classical complement pathway
0302 clinical medicine
law
Genes
Reporter
Humans
Receptor
skin and connective tissue diseases
Luciferases
Promoter Regions
Genetic
Molecular Biology
Transcription factor
Gene
Protein kinase C
Human T-lymphotropic virus 1
Activator (genetics)
BRCA1 Protein
Extra View
Estrogen Receptor alpha
NF-kappa B
Promoter
Cell Biology
Gene Products
tax
Molecular biology
Cell biology
Gene Expression Regulation
Neoplastic
030104 developmental biology
030220 oncology & carcinogenesis
Host-Pathogen Interactions
MCF-7 Cells
Suppressor
Tetradecanoylphorbol Acetate
Female
Tumor Suppressor p53-Binding Protein 1
hormones
hormone substitutes
and hormone antagonists
Developmental Biology
Signal Transduction
Popis: Interference with the expression and/or functions of the multifunctional tumor suppressor BRCA1 leads to a high risk of breast and ovarian cancers. BRCA1 expression is usually activated by the estrogen (E2) liganded ERα receptor. Activated ERα is considered as a potent transcription factor which activates various genes expression by 2 pathways. A classical pathway, ERα binds directly to E2-responsive elements (EREs) in the promoters of the responsive genes and a non-classical pathway where ERα indirectly binds with the appropriate gene promoter. In our previous study, HTLV-1Tax was found to strongly inhibit ERα induced BRCA1 expression while stimulating ERα induced ERE dependent genes. TPA is a strong PKC activator which found to induce the expression of HTLV-1. Here we examined the effect of TPA on the expression of BRCA1 and genes controlled by ERE region in MCF-7 cells and on Tax activity on these genes. Our results showed strong stimulatory effect of TPA on both BRCA1 and ERE expression without treatment with E2. Tax did not show any significant effect on these TPA activities. It seems that TPA activation of BRCA1 and ERE expression is dependent on PKC activity but not through the NFκB pathway. However, 53BP1 may be involved in this TPA activity because its overexpression significantly reduced the TPA stimulatory effect on BRCA1 and ERE expression. Additionally, our Chip assay results probably exclude possible involvement of ERα pathway in this TPA activity because TPA did not interfere with the binding of ERα to both BRCA1 promoter and ERE region.
Databáze: OpenAIRE
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