10831156

pubmed:Citation

4

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.

eng

IM

MEDLINE

0742-3098

Print

NLM

210-8

pubmed-meshheading:10831156-Blotting, Northern, pubmed-meshheading:10831156-Breast Neoplasms, pubmed-meshheading:10831156-Estradiol, pubmed-meshheading:10831156-Female, pubmed-meshheading:10831156-Humans, pubmed-meshheading:10831156-Melatonin, pubmed-meshheading:10831156-Protein Biosynthesis, pubmed-meshheading:10831156-Proteins, pubmed-meshheading:10831156-RNA, pubmed-meshheading:10831156-RNA, Messenger, pubmed-meshheading:10831156-Receptors, Cell Surface, pubmed-meshheading:10831156-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:10831156-Receptors, Estrogen, pubmed-meshheading:10831156-Receptors, Melatonin, pubmed-meshheading:10831156-Receptors, Progesterone, pubmed-meshheading:10831156-Transforming Growth Factor beta, pubmed-meshheading:10831156-Tumor Cells, Cultured, pubmed-meshheading:10831156-Tumor Suppressor Proteins

Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatonin.

Journal Article, Research Support, U.S. Gov't, P.H.S.