Artikel
Antiestrogens modulate MT1 melatonin receptor expression in breast and ovarian cancer cell lines
Suche in Medline nach
Autoren
Veröffentlicht: | 20. März 2006 |
---|
Gliederung
Text
Objective: An interaction between cellular estrogen response and melatonin signaling mediated by G-protein coupled receptors is present in breast cancer cells. In this study, the effect of antiestrogens on basal and melatonin-modulated expression of MT1 melatonin receptor in breast and ovarian cancer cells was examined.
Methods: For this purpose, effects of the selective estrogen receptor modulator tamoxifen and the pure antiestrogen ICI 182,780 on MT1 expression in estrogen receptor (ER) α-positive and -negative breast and ovarian cancer cell lines cultured in medium supplemented with 1 nM estradiol were assessed by Western blot analysis.
Results: We were able to detect expression of MT1 receptor in SK-OV-3 and OVCAR-3 cells and report its upregulation by melatonin in both ovarian cancer cell lines. MT1 expression was observed to be significantly weaker in ERα-positive MCF-7 and OVCAR-3 cells than in ERα-negative MDA-MB-231 and SK-OV-3 cells. Treatment with the pure antiestrogen ICI 182,780 increased MT1 receptor expression in OVCAR-3 ovarian cancer cells, but decreased MT1 expression in MCF-7 breast cancer cells. No effect of ICI 182,780 on MT1 expression was observed in the ERα-negative cell lines SK-OV-3 and MDA-MB-231. After treatment with 4-OH tamoxifen, downregulation of basal MT1 receptor expression in ERα-positive MCF-7 cells and inhibition of melatonin-induced upregulation of MT1 in OVCAR-3 ovarian cancer cells was observed. In contrast, treatment with 4-OH tamoxifen increased MT1 receptor level in ERα-negative SK-OV-3 ovarian cancer cells.
Conclusion: Our findings support the existence of a close interaction between estrogen and melatonin signaling. Moreover, our data suggests, that melatonin signaling is modulated by antiestrogens in breast and ovarian cancer cells.