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Molecular deficiency (ies) in MT 1 melatonin signaling pathway underlies the melatonin‐unresponsive phenotype in MDA ‐ MB ‐231 human breast cancer cells
Author(s) -
Mao Lulu,
Yuan Lin,
Xiang Shulin,
Zeringue Samantha B.,
Dauchy Robert T.,
Blask David E.,
Hauch Adam,
Hill Steven M.
Publication year - 2014
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/jpi.12117
Subject(s) - melatonin , cell growth , melatonin receptor , cell culture , estrogen receptor , biology , cancer cell , endocrinology , cancer research , signal transduction , receptor , medicine , apoptosis , breast cancer , cancer , microbiology and biotechnology , biochemistry , genetics
Melatonin has been shown repeatedly to inhibit the growth of human breast tumor cells in vitro and in vivo. Its antiproliferative effects have been well studied in MCF ‐7 human breast cancer cells and several other estrogen receptor α ( ER α )‐positive human breast cancer cell lines. However, the MDA ‐ MB ‐231 breast cancer cell line, an ER α ‐negative cell line widely used in breast cancer research, has been shown to be unresponsive to melatonin's growth‐suppressive effect in vitro. Here, we examined the effect of melatonin on the cell proliferation of several ER α ‐negative breast cancer cell lines including MDA ‐ MB ‐231, BT ‐20, and SK ‐ BR ‐3 cells. Although the MT 1 G‐protein‐coupled receptor is expressed in all three cell lines, melatonin significantly suppressed the proliferation of SK ‐ BR ‐3 cells without having any significant effect on the growth of MDA ‐ MB ‐231 and BT ‐20 cells. We confirmed that the MT 1‐associated G α proteins are expressed in MDA ‐ MB ‐231 cells. Further studies demonstrated that the melatonin unresponsiveness in MDA ‐ MB ‐231 cells may be caused by aberrant signaling downstream of the G α i proteins, resulting in differential regulation of ERK 1/2 activity.