Steroid sulfotransferase 2B1b (SULT2B1b) localization differences in African American and Caucasian breast tissue Free

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Sulfation is an important mechanism in the metabolism and inactivation of steroids in human normal and cancerous breast tissues. The SULT2A1 and SULT2B1b isoforms are responsible for the sulfation of hydroxysteroids. SULT2B1b is unique in that this isoform has been shown to localize to both the cytoplasm and the nucleus of breast and placental cells. SULT2A1 is not expressed in these cells. SULT2B1b is of interest in hormone responsive tissues and cancers because it is responsible for the sulfation of 3β-hydroxysteroids such as dehydroepiandrosterone (DHEA) and pregnenolone and prevents their conversion into estrogens and androgens. Rabbit anti-SULT2B1 polyclonal antibodies have been generated that are specific for the SULT2B1 isoforms and do not react with the other human SULTs. SULT2B1b has been immunohistochemically localized to the nuclei and cytoplasm of epithelial cells in normal breast and adenocarcinoma. Paraffin embedded normal and breast cancer tissues were obtained from the Tissue Procurement Service of the UAB Comprehensive Cancer. SULT2B1b was expressed heterogeneously in normal breast and breast cancer tissues. The differential localization of SULT2B1b in African American and Caucasian breast tissues was also investigated. SULT2B1b was expressed at a significantly higher level in the nuclei and cytoplasm of normal African American breast tissues as compared to Caucasians. The expression of SULT2B1b was also significantly increased in the cytoplasm of Caucasian cancer breast tissue. The increased levels of SULT2B1b observed in normal African American breast tissues as compared to Caucasian were not maintained in the breast cancer tissues. While SULT2B1b is the first SULT to be localized to the nucleus in human tissues, the function and mechanism for this localization remain unknown. However, because African Americans have higher levels of SULT2B1b expression and also have increased hormone levels, it is possible that hormone levels may play a role in regulating the levels of nuclear SULT2B1b expression and thereby the levels of active steroids in breast tissues. (Supported by PHS grant GM38953 to CNF)