Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatonin.
The estrogen receptor (ER)-positive MCF-7 human breast cancer cell line has been used extensively for the study of estrogen-responsive human breast cancer. However, various levels of estrogen responsiveness have been described in different stocks of MCF-7 cells. Because we have previously shown that the pineal hormone, melatonin, inhibits proliferation of MCF-7 cells and can modulate ER expression and transactivation, we investigated if various stocks of MCF-7 cells exhibit a differential responsiveness to the anti-proliferative effects of melatonin and the possible mechanisms involved. The MCF-7 stocks (M, O, H) were examined for: (1) mitogenic response to estradiol; (2) steady-state ER mRNA levels; (3) expression of the mt1 melatonin membrane receptor; (4) growth inhibition by melatonin; and (5) melatonin's modulation of expression of the ER and the estrogen-regulated genes, PgR, TGFbeta and pS2. For all of these parameters, there was a stock-specific response which showed: MCF-7M > MCF-7O > MCF-7H. These results demonstrate that there are significant differences in the responsiveness of various stocks of MCF-7 breast cancer cells to the growth-inhibitory effects of melatonin which can be correlated with both the level of ER mRNA expression and the degree of estrogen-responsiveness. These findings suggest that not only may these differences have some impact on the cells' estrogen-response pathway, but also that the primary growth-inhibitory effects of melatonin are transduced through the membrane-associated G-protein coupled mt1 melatonin receptor.
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- Tumor Suppressor Proteins
- Tumor Cells, Cultured
- Trefoil Factor-1
- Transforming Growth Factor beta
- Receptors, Progesterone
- Receptors, Melatonin
- Receptors, Estrogen
- Receptors, Cytoplasmic and Nuclear
- Receptors, Cell Surface
- RNA, Messenger
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Proteins
- Tumor Cells, Cultured
- Trefoil Factor-1
- Transforming Growth Factor beta
- Receptors, Progesterone
- Receptors, Melatonin
- Receptors, Estrogen
- Receptors, Cytoplasmic and Nuclear
- Receptors, Cell Surface
- RNA, Messenger