Premium
Melatonin modulation of estrogen‐regulated proteins, growth factors, and proto‐oncogenes in human breast cancer
Author(s) -
Molis Tina M.,
Spriggs Louaine L.,
Jupiter Yolanda,
Hill Steven M.
Publication year - 1995
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1995.tb00146.x
Subject(s) - melatonin , endocrinology , medicine , estrogen , estrogen receptor , biology , cell growth , breast cancer , cancer , biochemistry
The growth‐inhibitory actions of the pineal hormone, melatonin, on hu‐man breast tumor cells and the possible association between this inhibition and melatonin's down‐regulation of the estrogen receptor (ER) expression were exam‐ined in the ER‐positive, estrogen‐responsive MCF‐7 human breast tumor cell line. As previously reported, melatonin dramatically inhibits the growth of these breast tumor cells and down‐regulates ER levels in these cells, suggesting that the modu‐lation of ER may be an important mechanism by which melatonin inhibits breast cancer cell growth. In the present studies, Northern blot analysis was used to ex‐amine the expression of estrogen‐regulated transcripts known to be involved in es‐trogen's mitogenic actions. Melatonin, at a physiologic concentration (10 −9 M), rapidly, significantly, and, in some cases, transiently elevated the steady‐state mRNA levels of growth stimulatory products such as TGFα, c‐myc, and pS2, which are normally up‐regulated in response to estrogen. Conversely, melatonin decreased the expression of other factors normally up‐regulated by estrogen, such as progesterone receptor and c‐fos. Significant stimulation of the expression of the growth‐inhibitory factor TGFβ was seen with melatonin treatment, potentially sup‐porting the concept that melatonin's growth‐inhibitory activity is mediated through the breast tumor cells’estrogen‐response pathway. The early regulation of many of these products by melatonin suggests that mechanisms more rapid than the down‐regulation of ER are important in melatonin's modulation of their ex‐pression. However, the long‐term modulation of these transcripts (12–48 hr) may be heavily influenced by melatonin's down‐regulation of ER expression. These re‐sults clearly define the need for additional in depth studies to dissect the cellular events leading to melatonin‐induced growth inhibition in breast tumor cells.