Tamoxifen up-regulates c-erbB-2 expression in oestrogen-responsive breast cancer cells in vitro.
Expression of the c-erbB-2 proto-oncogene is inhibited by oestrogens in oestrogen-responsive human breast cancer cells, at both mRNA and protein level. Here we report that, where the regulation of c-erbB-2 is concerned, tamoxifen displays a full anti-oestrogenic activity, enhancing the expression of c-erbB-2 in oestrogen receptor-positive cells cultured with untreated fetal calf serum or reversing the inhibitory effect of added oestrogens. Meanwhile, tamoxifen strongly inhibited cell growth. Tamoxifen was inactive on both c-erbB-2 expression and growth of oestrogen receptor-negative cells. These results may have important implications to explain occasional failure of tamoxifen therapy in oestrogen receptor-positive breast cancers.
Dipartimento di Biologia Animale, University of Torino, Italy.
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S
Antoniotti
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P
Maggiora
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C
Dati
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M
De Bortoli
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000473:pathology; D015854:Up-Regulation
D004965:Estrogen Antagonists; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; C000715470:MAS1 protein, human