One of the most widely used and effective agents in the treatment of metastatic breast cancer is the anti-estrogen tamoxifen. The efficacy of therapy with this low toxic anti-honnonal drug is based on the dependence of many breast tumors on estrogen for growth and survival. The mechanism of action of anti-estrogens relies on their ability to compete with estrogens for binding to the estrogen receptor (ER) and to block cell proliferation in honnone-dependent cells. Many breast carcinomas express the estrogen receptor a (ERa) and are eligible for treatment with tamoxifen. Nearly 50% of ER-positive tumors respond to tamoxifen treatment by tumor regression or long-term disease stabilization. However, the response duration is limited due to the inevitable development of tamoxifen-resistant tumors (acquired resistance). Moreover, half of the patients with ER-positive tumors do not respond to tamoxifen treatment (intrinsic resistance). Tamoxifen resistant proliferation of human breast cancer cells results from yet umesolved mechanisms. Presumably, there are several mechanisms capable of bypassing estrogen dependency and causing tamoxifen resistance. The working hypothesis for this study was that (epi)genetic alterations occurring in the tumor cells might playa role in intrinsic and acquired resistance to tamoxifen treatment. In search of genes involved in tamoxifen resistance of breast cancer cells, an ill vitro model system has been developed which mimics the clinical situation. Accordingly, the breast cancer ant-estrogen resistance I (BCARI) locus has been identified, harboring a gene involved in tamoxifen resistance in vitro. The objective of this study was to identify and characterize the gene in the BCARI locus, and to delineate the importance of BCARI in clinical tamoxifen resistance.

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Nederlandse Kankerbestrijding (KWF)
J.W. Oosterhuis (Wolter) , D. Bootsma (Dirk)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam

van der Flier, S. (2000, June 21). BCAR1and Anti-estrogen Resistance of Human Breast Cancer. Retrieved from