The Galphai and Galphaq proteins mediate the effects of melatonin on steroid/thyroid hormone receptor transcriptional activity and breast cancer cell proliferation.

Journal of Pineal Research
Ling LaiSteven M Hill

Abstract

Melatonin, via its MT1 receptor, but not the MT2 receptor, can modulate the transcriptional activity of various nuclear receptors - estrogen receptor alpha (ERalpha) and retinoic acid receptor alpha (RARalpha), but not ERbeta- in MCF-7, T47D, and ZR-75-1 human breast cancer cell lines. The anti-proliferative and nuclear receptor modulatory actions of melatonin are mediated via the MT1 G protein-coupled receptor expressed in human breast cancer cells. However, the specific G proteins and associated pathways involved in the nuclear receptor transcriptional regulation by melatonin are not yet clear. Upon activation, the MT1 receptor specifically couples to the G(alphai2), G(alphai3), G(alphaq), and G(alphall) proteins, and via activation of G(alphai2) proteins, melatonin suppresses forskolin-induced 3',5'-cyclic adenosine monophosphate production, while melatonin activation of G(alphaq), is able to inhibit phospholipid hydrolysis and ATP's induction of inositol triphosphate production in MCF-7 breast cancer cells. Employing dominant-negative and dominant-positive) forms of these G proteins, we demonstrate that G(alphai2) proteins mediate the suppression of estrogen-induced ERalpha transcriptional activity by melatonin, while the G...Continue Reading

References

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Citations

Jul 21, 2011·Journal of Mammary Gland Biology and Neoplasia·Steven M HillTamika Duplesis
Mar 10, 2011·Journal of Receptor and Signal Transduction Research·Olga RögelspergerTheresia Thalhammer
Aug 4, 2012·Bioorganic & Medicinal Chemistry·M Concepción LozadaArturo Jiménez-Corona
Jun 26, 2009·Journal of Pineal Research·O RögelspergerT Thalhammer
Jul 9, 2010·Journal of Pineal Research·Lulu MaoSteven M Hill
Jan 8, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jian YaoXianghuo He
Apr 17, 2015·Endocrine-related Cancer·Steven M HillDavid E Blask
Jan 17, 2012·Molecular and Cellular Endocrinology·Radomir M SlominskiAndrzej T Slominski
Jan 6, 2010·Integrative Cancer Therapies·Steven M HillLulu Mao
Mar 29, 2013·International Journal of Molecular Sciences·Elmar PeschkeEckhard Mühlbauer
Sep 8, 2017·International Journal of Molecular Sciences·Federica Lo SardoSabrina Strano
Sep 26, 2012·Cellular and Molecular Life Sciences : CMLS·Sara ProiettiMariano Bizzarri
Aug 29, 2014·Cellular Oncology (Dordrecht)·Ekaterini Christina TampakiGregory Kouraklis
Mar 28, 2016·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Elaheh NooshinfarMohammad Esmaeil Akbari
Jun 26, 2020·Journal of Cancer Research and Clinical Oncology·Saptadip Samanta

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