Restoration of estrogen responsiveness by blocking the HER-2/neu pathway.
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.
Witters
Lois
L
Department of Medicine, Penn State College of Medicine, Hershey, PA 17033, USA.
Engle
Linda
L
Lipton
Allan
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013629:Tamoxifen / Q000494:pharmacology*; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D004958:Estradiol; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D000068878:Trastuzumab