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Lewis-Wambi JS , Jordan VC
Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit?
Breast Cancer Res. 2009 ;11(3) :206
PMID: 19519952    PMCID: PMC2716493   
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Abstract
The link between estrogen and the development and proliferation of breast cancer is well documented. Estrogen stimulates growth and inhibits apoptosis through estrogen receptor-mediated mechanisms in many cell types. Interestingly, there is strong evidence that estrogen induces apoptosis in breast cancer and other cell types. Forty years ago, before the development of tamoxifen, high-dose estrogen was used to induce tumor regression of hormone-dependent breast cancer in post-menopausal women. While the mechanisms by which estrogen induces apoptosis were not completely known, recent evidence from our laboratory and others demonstrates the involvement of the extrinsic (Fas/FasL) and the intrinsic (mitochondria) pathways in this process. We discuss the different apoptotic signaling pathways involved in E2 (17beta-estradiol)-induced apoptosis, including the intrinsic and extrinsic apoptosis pathways, the NF-kappaB (nuclear factor-kappa-B)-mediated survival pathway as well as the PI3K (phosphoinositide 3-kinase)/Akt signaling pathway. Breast cancer cells can also be sensitized to estrogen-induced apoptosis through suppression of glutathione by BSO (L-buthionine sulfoximine). This finding has implications for the control of breast cancer with low-dose estrogen and other targeted therapeutic drugs.
Notes
Lewis-Wambi, Joan S Jordan, V Craig CA89018/CA/NCI NIH HHS/United States K01 CA120051-01A2/CA/NCI NIH HHS/United States P30 CA006927/CA/NCI NIH HHS/United States R01 GM067156/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review England Breast cancer research : BCR Breast Cancer Res. 2009;11(3):206. Epub 2009 May 29.