Hormonal regulation of c-erbB-2 oncogene expression in breast cancer cells.
Expression of the c-erbB-2 (neu, HER-2) oncogene is found to be subjected to hormonal and developmental regulation in normal as well as neoplastic mammary cells. We have previously reported that estrogens inhibit c-erbB-2 expression at both the mRNA and protein level in estrogen receptor (ER)-positive, but not in ER-negative, breast cancer cell lines. Reversion of c-erbB-2 inhibition is seen with tamoxifen. The effect on c-erbB-2 expression of several other hormones and factors, which influence mammary cell growth and differentiation, has been studied. Our observations indicate that, in normal and neoplastic mammary cells, c-erbB-2 expression is inversely related to cell proliferation. While estrogens, anti-estrogens and cAMP clearly regulate c-erbB-2 mRNA levels, epidermal growth factor dramatically decreases the c-erbB-2 protein without affecting the level of c-erbB-2 mRNA. Therefore, different signals converging in terms of cell proliferation regulate c-erbB-2 expression by different molecular mechanisms.
Department of Animal Biology, University of Turin, Torino, Italy.
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De Bortoli
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Dati
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Antoniotti
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Maggiora
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Sapei
D001943:Breast Neoplasms / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006728:Hormones / Q000502:physiology*; D006801:Humans; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases
D006728:Hormones; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases