INVOLVEMENT OF VARIOUS TRANSCRIPTIONAL FACTORS IN HTLV-1 TAX ONCOPROTEIN EFFECTS ON THE DIFFERENT ESTROGEN-INDUCED-ER α-MEDIATED TRANSCRIPTIONAL ACTIVITIES

The activated estrogen (E2) receptor alpha (ERα) is a potent transcription factor that is involved in the activation of various genes by two different pathways; a classical and non-classical. In the classical pathway, ERα binds directly to E2-responsive elements (EREs) located in the appropriate genes promoters and then stimulates the transcription of these genes. However, in the non-classical pathways, the ERα can indirectly bind with promoters lacking these ERE elements, like the promoter of BRCA1, and enhance their activity. In the case of BRCA1, the E2 ligated ERα activates BRCA1 expression by interacting with the jun/fos complex bound to the AP-1 site residing in the BRCA1 promoter. Interference with the expression and/or functions of the multifunctional tumor suppressor, BRCA1, leads to high risk of breast or/and ovarian cancer. HTLV-1Tax which is known as oncoprotein, was found, in our previous study, to strongly inhibit BRCA1 expression by preventing the binding of the E2–ERα complex to BRCA1 promoter. Here we examined Tax effect on ERα induced activation of ERE expression by testing its influence on E2-induced expression of ERE promoter-driven luciferase reporter (ERE-Luc). We examined also the involvement of different cofactors in these Tax activities. Our findings showed that E2 profoundly stimulated this reporter expression by liganding to ERα, which consequently associated with ERE region and that HTLV-1Tax significantly induced this stimulation. This result is highly interesting because in our previous study Tax was found to strongly block the E2-ERα-mediated activation of BRCA1 expression. We found that ERα producing a big complex with other cofactors by recruiting various them in the nucleus before binding to the ERE region. We also found that only part of the reqruited cofactors are required for the transcriptional activity of ERα complex.