title: Knockdown of receptor for advanced glycation end products attenuate 17α-ethinyl-estradiol dependent proliferation and survival of MCF-7 breast cancer cells.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, Indian Institute of Science Education and Research (IISER) Mohali Sector 81, SAS Nagar, Manauli, 140306, Punjab, India.
authors.forename: Kusum
authors.initials: K
authors.lastname: Lata
authors.affiliation: 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.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Mukherjee
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival; D019938:Cyclin D1 / Q000032:analysis; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011960:Receptors, Estrogen / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*
chemical_list: C530104:CCND1 protein, human; C490917:ESRRG protein, human; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011960:Receptors, Estrogen; D011971:Receptors, Immunologic; D019938:Cyclin D1; D004997:Ethinyl Estradiol; D051057:Proto-Oncogene Proteins c-akt
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