Kusum Lata1, Tapan K Mukherjee2. 1. Department of Biology, Indian Institute of Science Education and Research (IISER) Mohali Sector 81, SAS Nagar, Manauli, 140306, Punjab, India. 2. Department of Biology, Indian Institute of Science Education and Research (IISER) Mohali Sector 81, SAS Nagar, Manauli, 140306, Punjab, India; Department of Biotechnology, Maharishi Markendeshwar University (A deemed University), Mullana, Haryana-133203, India. Electronic address: tapanmu@yahoo.com.
Abstract
BACKGROUND: 17α-ethinyl-estradiol (17α-EE), a synthetic estrogen is the world's most widely and commonly used orally bioactive estrogen. Currently, 17α-EE is in use in all formulations of contraceptive pills and is implicated in the complication of breast cancer. Receptor for advanced glycation end products (RAGE) is a cell surface immunoglobulin class of molecule. RAGE is involved in the complication of various cancers. METHODS AND RESULTS: This study indicates that treatment of MCF-7 breast cancer cells with 17α-EE enhances the expression of estrogen receptor related receptor gamma (ERRγ), followed by enhanced level of oxidative stress and subsequent activation of the transcription factor, nuclear factor kappa-B (NF-кB), leading to increase in RAGE expression. RAGE thus expressed by 17α-EE treatment causes further enhancement of the oxidative stress which, in turn, activates expression of cell cycle protein cyclin D1 and subsequent induction of MCF-7 breast cancer cell proliferation. RAGE also enhanced phosphorylation of prosurvival protein AKT and increased expression of Bcl2, an antiapoptotic protein. CONCLUSION: In MCF-7 breast cancer cells, 17α-EE-ERRγ interaction induces the expression of RAGE, which in turn, enhances the number of MCF-7 breast cancer cells through a multiprong action on the divergent molecules like cyclin D1, AKT and Bcl2. GENERAL SIGNIFICANCE: This is the first report which explains the intermediate role of ERRγ in the 17α-EE dependent RAGE expression in MCF-7 breast cancer cells. This report for the first time explains that RAGE is important not only for MCF-7 breast cancer cell proliferation but also for its survival and anti-apoptotic activities.
BACKGROUND: 17α-ethinyl-estradiol (17α-EE), a synthetic estrogen is the world's most widely and commonly used orally bioactive estrogen. Currently, 17α-EE is in use in all formulations of contraceptive pills and is implicated in the complication of breast cancer. Receptor for advanced glycation end products (RAGE) is a cell surface immunoglobulin class of molecule. RAGE is involved in the complication of various cancers. METHODS AND RESULTS: This study indicates that treatment of MCF-7 breast cancer cells with 17α-EE enhances the expression of estrogen receptor related receptor gamma (ERRγ), followed by enhanced level of oxidative stress and subsequent activation of the transcription factor, nuclear factor kappa-B (NF-кB), leading to increase in RAGE expression. RAGE thus expressed by 17α-EE treatment causes further enhancement of the oxidative stress which, in turn, activates expression of cell cycle protein cyclin D1 and subsequent induction of MCF-7 breast cancer cell proliferation. RAGE also enhanced phosphorylation of prosurvival protein AKT and increased expression of Bcl2, an antiapoptotic protein. CONCLUSION: In MCF-7 breast cancer cells, 17α-EE-ERRγ interaction induces the expression of RAGE, which in turn, enhances the number of MCF-7 breast cancer cells through a multiprong action on the divergent molecules like cyclin D1, AKT and Bcl2. GENERAL SIGNIFICANCE: This is the first report which explains the intermediate role of ERRγ in the 17α-EE dependent RAGE expression in MCF-7 breast cancer cells. This report for the first time explains that RAGE is important not only for MCF-7 breast cancer cell proliferation but also for its survival and anti-apoptotic activities.
Keywords:
17-alpha-ethinyl estradiol; Estrogen receptor related receptor gamma; MCF-7 breast cancer cells proliferation and survival; Reactive oxygen species; Receptor for advanced glycation product
Authors: Mohd W Nasser; Nissar Ahmad Wani; Dinesh K Ahirwar; Catherine A Powell; Janani Ravi; Mohamad Elbaz; Helong Zhao; Laura Padilla; Xiaoli Zhang; Konstantin Shilo; Michael Ostrowski; Charles Shapiro; William E Carson; Ramesh K Ganju Journal: Cancer Res Date: 2015-01-08 Impact factor: 12.701
Authors: Katherine R Walter; Marvella E Ford; Mathew J Gregoski; Rita M Kramer; Kendrea D Knight; Laura Spruill; Lourdes M Nogueira; Bradley A Krisanits; Van Phan; Amanda C La Rue; Michael B Lilly; Stefan Ambs; King Chan; Tonya F Turner; Heidi Varner; Shweta Singh; Jaime Uribarri; Elizabeth Garrett-Mayer; Kent E Armeson; Ebony J Hilton; Mark J Clair; Marian H Taylor; Andrea M Abbott; Victoria J Findlay; Lindsay L Peterson; Gayenell Magwood; David P Turner Journal: Breast Cancer Res Treat Date: 2018-10-27 Impact factor: 4.624