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Hormonal regulation of c-erbB-2 oncogene expression in breast cancer cells
M De Bortoli1, C Dati, S Antoniotti
1Department of Animal Biology, University of Turin, Torino, Italy.
Abstract:
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.
Insights
Hormones like estrogens and tamoxifen regulate the c-erbB-2 oncogene in breast cells. Its expression inversely correlates with cell proliferation, influenced by various growth factors through distinct molecular pathways.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- The c-erbB-2 (HER-2) oncogene plays a role in mammary cell development and cancer.
- Estrogen receptor (ER)-positive breast cancer cells show hormonal regulation of c-erbB-2 expression.
- Previous studies indicated estrogens inhibit c-erbB-2, with tamoxifen reversing this effect.
Purpose of the Study:
- To investigate the hormonal and developmental regulation of c-erbB-2 expression in mammary cells.
- To examine the impact of various hormones and growth factors on c-erbB-2 expression.
- To understand the molecular mechanisms underlying c-erbB-2 regulation in relation to cell proliferation.
Main Methods:
- Studied c-erbB-2 expression at mRNA and protein levels in different breast cancer cell lines.
- Utilized various hormones (estrogens, anti-estrogens) and growth factors (epidermal growth factor).
- Assessed the relationship between c-erbB-2 expression and cell proliferation rates.
Main Results:
- Estrogens and anti-estrogens regulate c-erbB-2 mRNA levels, affecting ER-positive cells.
- Epidermal growth factor reduces c-erbB-2 protein without altering mRNA levels.
- c-erbB-2 expression is inversely correlated with mammary cell proliferation.
Conclusions:
- Hormonal and developmental factors significantly regulate c-erbB-2 oncogene expression.
- Different signaling pathways converge to control c-erbB-2 expression via distinct molecular mechanisms.
- Understanding these regulatory mechanisms is crucial for breast cancer research and therapy.