Researchers Map Route from Estrogen Receptors to Breast Cancer

Researchers have charted the path that links the estrogen receptors that bind this hormone and regulate normal breast cell growth and development to molecular events that result in the unregulated growth of cancer cells.

Approximately 70% of breast tumors contain estrogen receptors and are dependent on estrogen for their growth. These estrogen receptor positive breast cancers are sensitive to a class of drugs known as selective estrogen receptor modulators (SERMS), including drugs such as tamoxifen. Breast tumors lacking estrogen receptors are not affected by estrogen antagonist drugs, and thus generally do not respond to treatment.

Investigators at Emory University (Atlanta, GA, USA) identified the protein MTA3, an estrogen-dependent component of the Mi-2/NuRD transcriptional co-repressor in breast epithelial cells, and demonstrated that MTA3 constituted a key component of an estrogen-dependent pathway regulating growth and differentiation. The absence of estrogen receptor or of MTA3 led to aberrant expression of the transcriptional repressor Snail, and aberrant Snail expression resulted in loss of expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. These findings were published in the April 18, 2003, issue of Cell.

"Our findings have important consequences for the treatment of patients with drugs that target the estrogen receptor, and they provide a mechanistic explanation for a pathway that may lead to cancer progression,” explained senior author Dr. Paul A. Wade, assistant professor of pathology and laboratory medicine at Emory University. "A number of compounds currently in clinical trials for breast cancer, osteoporosis and other disorders target the estrogen receptor and turn it off in particular cells and tissues. Understanding how these compounds affect the estrogen receptor pathway and the potentially negative results from loss of the proteins that regulate cellular architecture, is very important in assessing the safety of these drugs and in developing other effective therapies for breast cancer.”



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