Dumas Nicole A, He Dongning, Frost Andra R, Falany Charles N
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):171-7. doi: 10.1016/j.jsbmb.2008.05.006. Epub 2008 Jun 8.
Breast cancer (BC) is the most commonly diagnosed cancer among American women; however, the development of post-menopausal BC is significantly lower in African Americans as compared to Caucasians. Hormonal stimulation is important in BC development and differences in the conversion of dehydroepiandrosterone (DHEA) into estrogens may be involved in the lower incidence of post-menopausal BC in African American women. DHEA sulfation by sulfotransferase 2B1b (SULT2B1b) is important in regulating the conversion of DHEA into estrogens in tissues. SULT2B1b is localized in both cytosol and nuclei of some tissues including cancerous and associated-normal breast tissue. Immunohistochemical staining was used to evaluate the total expression and subcellular localization of SULT2B1b in African American and Caucasian breast tissues. Cell fractionation, immunoblot analysis and sulfation assays were used to characterize the subcellular expression and activity of SULT2B1b in BC tissues and T-47D breast adenocarcinoma cells. Immunohistochemical analysis of SULT2B1b showed that African Americans had a significantly greater amount of SULT2B1b in epithelial cells of associated-normal breast tissue as compared to Caucasians. Also, more SULT2B1b in African American associated-normal breast epithelial cells was localized in the nuclei than in Caucasians. Equivalent levels of SULT2B1b were detected in breast adenocarcinoma tissues from both African American and Caucasian women. Nuclei isolation and immunoblot analysis of both BC tissue and human T-47D breast adenocarcinoma cells demonstrated that SULT2B1b is present in nuclei and cytoplasm.
乳腺癌(BC)是美国女性中最常被诊断出的癌症;然而,与白种人相比,非裔美国绝经后乳腺癌的发病率显著更低。激素刺激在乳腺癌发展中很重要,脱氢表雄酮(DHEA)向雌激素转化的差异可能与非裔美国女性绝经后乳腺癌发病率较低有关。硫酸转移酶2B1b(SULT2B1b)介导的DHEA硫酸化在调节组织中DHEA向雌激素的转化中起重要作用。SULT2B1b定位于包括癌性及相关正常乳腺组织在内的一些组织的细胞质和细胞核中。采用免疫组织化学染色评估SULT2B1b在非裔美国人和白种人乳腺组织中的总表达及亚细胞定位。利用细胞分级分离、免疫印迹分析和硫酸化测定来表征SULT2B1b在乳腺癌组织和T-47D乳腺腺癌细胞中的亚细胞表达及活性。SULT2B1b的免疫组织化学分析表明,与白种人相比,非裔美国人相关正常乳腺组织上皮细胞中的SULT2B1b含量显著更高。此外,非裔美国人相关正常乳腺上皮细胞中更多的SULT2B1b定位于细胞核,而白种人则不然。在非裔美国人和白种人女性的乳腺腺癌组织中检测到的SULT2B1b水平相当。对乳腺癌组织和人T-47D乳腺腺癌细胞进行细胞核分离和免疫印迹分析表明,SULT2B1b存在于细胞核和细胞质中。