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Tamoxifen up-regulates c-erbB-2 expression in oestrogen-responsive breast cancer cells in vitro
S Antoniotti1, P Maggiora, C Dati
1Dipartimento di Biologia Animale, University of Torino, Italy.
Abstract:
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.
Insights
Tamoxifen, an anti-oestrogen drug, enhances c-erbB-2 expression in oestrogen receptor-positive breast cancer cells, inhibiting their growth. This finding may explain treatment failures in some breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Oestrogens inhibit c-erbB-2 proto-oncogene expression in human breast cancer cells.
- c-erbB-2 proto-oncogene plays a crucial role in cell proliferation and cancer development.
Purpose of the Study:
- To investigate the effect of tamoxifen on c-erbB-2 expression in oestrogen receptor-positive and negative breast cancer cells.
- To understand the role of tamoxifen in regulating c-erbB-2 and its impact on cell growth.
Main Methods:
- Cell culture of oestrogen receptor-positive and negative human breast cancer cells.
- Analysis of c-erbB-2 mRNA and protein expression levels.
- Assessment of cell growth inhibition by tamoxifen.
Main Results:
- Tamoxifen demonstrated full anti-oestrogenic activity, enhancing c-erbB-2 expression in oestrogen receptor-positive cells.
- Tamoxifen reversed oestrogen's inhibitory effect on c-erbB-2 and strongly inhibited cell growth.
- Tamoxifen had no effect on c-erbB-2 expression or growth in oestrogen receptor-negative cells.
Conclusions:
- Tamoxifen's regulation of c-erbB-2 expression contributes to its anti-cancer effects in oestrogen receptor-positive breast cancer.
- These findings may elucidate the mechanisms behind tamoxifen therapy failure in certain breast cancer cases.