Restoration of estrogen responsiveness by blocking the HER-2/neu pathway |
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Authors: | Witters Lois Engle Linda Lipton Allan |
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Institution: | Department of Medicine, Penn State College of Medicine, Hershey, PA 17033, USA. |
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Abstract: | HER-2/neu gene amplification or protein overexpression is evident in 20-30% of primary breast cancers. Its amplification correlates with poor prognosis. There appears to be an association between HER-2/neu overexpression and estrogen independence. The MCF-7 human breast carcinoma cell line is estrogen-dependent and sensitive to the anti-estrogen, tamoxifen (TAM). This line, when transfected with the HER-2/neu gene, becomes estrogen-independent and resistant to TAM. Blockade of the HER-2/neu receptor with 1-5 nM of the humanized HER-2/neu antibody, Herceptin, restored estrogen, as well as TAM, sensitivity. These results suggest that Herceptin or similar drugs may restore estrogen sensitivity and the administration of a HER-2/neu inhibitor with an anti-estrogen to premenopausal patients should be considered. |
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