Membrane Estrogen and HER-2 Receptors in Human Breast Cancer

摘要

Patients with breast cancers that express estrogen receptor (ER) commonly receive antiestrogen therapy. The efficacy of this treatment depends on tight regulation of breast growth by estrogen. However, as breast cancers progress, they often become resistant to estrogens, and%most patients no longer respond to antiestrogen therapy. New antiestrogen treatment options are needed, and alternative therapies may derive from findings showing that some ER molecules occur in plasma membranes of breast cancer cells and interact with transmembrane HER-2 growth factor receptors. Expression of HER-2 receptors occurs in many breast cancers, and the protein kinase activity of HER-2 may modulate ligand-independent activation of ER. Active cross-communication between ER and HER-2 receptors occurs in breast tumors, leading to promotion of cancer growth. Thus, this axis may offer a new target for therapeutic intervention. We have partially purified a membrane-associated form of ER in breast cancer cells and have evidence that it promotes tumor growth. Using this novel signaling pathway as a target, we have assessed new treatments to prevent cancer progression in models of human breast cancer. Since HER-2 overexpression in breast cancer is associated with the failure of antiestrogen therapy, dual targeting of HER-2 and ER signaling may offer a new therapeutic strategy to assess in future clinical trials.