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

• DOI: 10.1034/j.1600-079x.2000.280403.x
• Publication Date: 2003-11-02T17:05:18Z
• Authors: Prahlad T. Ram; Lin Yuan; Jun Dai; Todd Kiefer; Diane M. Klotz; Louaine L. Spriggs; Steven M. Hill
• Keywords: 0303 health sciences; Estradiol; Tumor Suppressor Proteins; Receptors, Melatonin; Proteins; Receptors, Cytoplasmic and Nuclear; Breast Neoplasms; Receptors, Cell Surface; Blotting, Northern; 3. Good health; 03 medical and health sciences; Receptors, Estrogen; Transforming Growth Factor beta; Protein Biosynthesis; Tumor Cells, Cultured; Humans; RNA; Female; Trefoil Factor-1; RNA, Messenger; Receptors, Progesterone; 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, TGFβ and pS2. For all of these parameters, there was a stock‐specific response which showed: MCF‐7M>MCF‐7O>MCF‐7 H. 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.