Breast cancer research and treatment
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Breast Cancer Res. Treat. · Sep 2012
Comparative StudyMolecular characteristics and prognostic features of breast cancer in Nigerian compared with UK women.
Although breast cancer (BC) incidence is lower in African-American women compared with White-American, in African countries such as Nigeria, BC is a common disease. Nigerian women have a higher risk for early-onset, with a high mortality rate from BC, prompting speculation that risk factors could be genetic and the molecular portrait of these tumours are different to those of western women. In this study, 308 BC samples from Nigerian women with complete clinical history and tumour characteristics were included and compared with a large series of BC from the UK as a control group. ⋯ Nigerian women showed significantly poorer outcome after development of BC compared with UK women. This study demonstrates that there are possible genetic and molecular differences between an indigenous Black population and a UK-based series. The basal-like, triple negative and BRCA1 dysfunction groups of tumours identified in this study may have implications in the development of screening programs and therapies for African patients and families that are likely to have a BRCA1 dysfunction, basal like and triple negative.
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Breast Cancer Res. Treat. · Sep 2012
Serum and glucocorticoid-regulated kinase 1 (SGK1) activation in breast cancer: requirement for mTORC1 activity associates with ER-alpha expression.
Mammalian target of rapamycin (mTOR) is an attractive target for cancer treatment. While rapamycin and its derivatives (e.g., everolimus) have been shown to inhibit mTOR signaling and cell proliferation in preclinical models of breast cancer, mTOR inhibition has demonstrated variable clinical efficacy with a trend toward better responses in estrogen receptor alpha positive (ERα+) compared to ERα negative (ERα-) tumors. Recently, serum- and glucocorticoid-regulated kinase 1 (SGK1) was identified as a substrate of mTOR kinase activity. ⋯ In addition, either depleting SGK1 with shRNA or inhibiting SGK1 with GSK650394A preferentially sensitized MDA-MB-231 cells to rapamycin. Finally, we found that rapamycin-sensitive SGK1-Ser422 phosphorylation required ERα expression in MCF-7 derived cell lines. Therefore, targeting SGK1 activity may improve the efficacy of rapamycin and its analogs in the treatment of ERα- breast cancer.