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Breast cancer is one of the most frequently diagnosed cancers among women, with an estimated 184,450 new cases of invasive disease and 40,930 deaths in 2008. There is strong evidence that estrogen plays a role in its development and progression. Estrogen is produced by the ovaries and other tissues of the body, using an enzyme called aromatase. Aromatase inhibitors (AIs) can help block the growth of estrogen-dependent tumors by lowering the amount of estrogen in the body. AIs do not block estrogen production by the ovaries, but they can block other tissues from making this hormone once a women has reached menopause. AIs are currently accepted as the standard care for the treatment of estrogen receptor (ER)-positive breast cancer. Unfortunately, one of the consequences of long term estrogen deprivation (i.e. aromatase inhibition therapy) is the development of drug resistance. In order to further explore the development of acquired resistance to AIs, my laboratory has developed a panel of long-term estrogen deprived (LTED) breast cancer cell lines (i.e. MCF-7:5C, MCF-7:2A, MCF-7:ED) that have been adapted to grow under estrogen-depleted conditions. An interesting phenotype of these LTED cells is that they grow robustly in the absence of estrogen (i.e. hormone-independent), but undergo apoptosis in the presence of physiological concentrations of estrogen. The goal of my laboratory is to investigate the new biology of estrogen action in these LTED breast cancer cells and assess the mechanism(s) by which estrogen switches from being a growth stimulus (cancer-causing agent) to a killing (i.e. apoptotic) agent. We are also interested in studying whether long term estrogen deprivation increases the invasiveness and metastatic potential of breast cancer cells in vivo and in vitro.

1. Lewis-Wambi JS, Jordan VC. Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit? Breast Cancer Res. 2009;11:206. PubMed
2. Lewis-Wambi JS, Swaby RR, Helen K, Jordan VC. Potential of L-buthionine sulfoximine to enhance the apoptotic action of estradiol to reverse acquired antihormonal resistance in metastatic breast cancer. J Steroid Biochem Mol Biol.2009;114:33-9. PubMed
3. Lewis-Wambi JS, Kim HR, Wambi C, Patel R, Pyle J, Klein-Szanto AJ, Jordan VC. Buthionine sulfoximine sensitizes antihormone-resistant human breast cancer cells to estrogen-induced apoptosis. Breast Cancer Res. 2008;10:R104. PubMed
4. Lewis-Wambi JS, Cunliffe HE, Kim HR, Willis AL, Jordan VC. Overexpression of CEACAM6 promotes migration and invasion of estrogen deprived breast cancer cells. Eur J Cancer. 2008;44:1770-9. PubMed
5. Lewis JS, Meeke K, Osipo C, Ross EA, Kidawi N, Li T, Bell E, Chandel NS, Jordan VC. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation. J Natl Cancer Inst. 2005; 97:1746-59. PubMed