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.
Ram
P T
PT
Department of Anatomy, Tulane University School of Medicine, New Orleans, Lousiana 70112, USA.
Yuan
L
L
Dai
J
J
Kiefer
T
T
Klotz
D M
DM
Spriggs
L L
LL
Hill
S M
SM
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D044094:Receptors, Melatonin; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D044094:Receptors, Melatonin; D011980:Receptors, Progesterone; C051838:TFF1 protein, human; D016212:Transforming Growth Factor beta; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D004958:Estradiol; D012313:RNA; D008550:Melatonin