As a society publisher, everything we do is to support the scientific community – so you can trust us to always act in your best interests, and get your work the international recognition that it deserves.An article , which mentions Application of 19771-63-2, molecular formula is C4H5NO3S. The compound – (R)-2-Oxothiazolidine-4-carboxylic acid played an important role in people’s production and life., Application of 19771-63-2
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.
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Quinuclidine – Wikipedia,
Quinuclidine | C7H686N | ChemSpider