Related Products of 19771-63-2, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 19771-63-2, molcular formula is C4H5NO3S, introducing its new discovery.
New insights into estrogenic regulation of O6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-alpha and MGMT proteins by fulvestrant or O6-benzylguanine indicates fresh avenues for therapy
Endocrine therapy using estrogen receptor-alpha (ER-alpha) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of ER-alpha with O6-methylguanine DNA methyltransferase (MGMT), a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The ER-alpha -positive breast cancer cell lines (MCF-7, T47D) and ER- negative cell lines (MDAMB- 468, MDAMB-231), and established inhibitors of ER-alpha and MGMT, namely, ICI-182,780 (Faslodex) and O6-benzylguanine, respectively, were used to study MGMT-ER interactions. The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements (EREs) and two antioxidant-responsive elements (AREs). MGMT expression was upregulated by estrogen, downregulated by tamoxifen in Western blot and promoter-linked reporter assays. Similarly, both transient and stable transfections of Nrf-2 (nuclear factor-erythroid 2-related factor-2) increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this drugresistance determinant. Of the different ER-alpha antagonists tested, the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMTactivity in a dose, time and ER-alpha dependent manner, similar to O6-benzylguanine. Interestingly, fulvestrant exposure led to a degradation of both ER-alpha and MGMT proteins and O6-benzylguanine also induced a specific loss of ER-alpha and MGMT proteins in MCF-7 and T47D breast cancer cells with similar kinetics. Immunoprecipitation revealed a specific association of ER-alpha and MGMT proteins in breast cancer cells. Furthermore, silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and ER-alpha proteins. The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated. Fulvestrant enhanced the cytotoxicity of MGMT-targeted alkylating agents, namely, temozolomide and BCNU by 3 to 4-fold in ER-alpha positive cells, but not in ER-negative cells.We conclude that MGMTand ER-alpha proteins exist as a complex and are co-targeted for ubiquitin-conjugation and subsequent proteasomal degradation. The findings offer a clear rationale for combining alkylating agents with endocrine therapy.
The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 19771-63-2 is helpful to your research. Related Products of 19771-63-2
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