Xenoestrogen regulation of ERα/ERβ balance in hormone-associated cancers.
The hormone 17β-estradiol (E2) contributes to body homeostasis maintenance by regulating many different physiological functions in both male and female organs. E2 actions in reproductive and non-reproductive tissues rely on a complex net of nuclear and extra-nuclear signal transduction pathways triggered by at least two estrogen receptor subtypes (ERα and ERβ). Consequently, the de-regulation of E2:ER signaling contributes to the pathogenesis of many diseases including cancer. Among other factors, the ERα/ERβ ratio is considered one of the pivotal mechanisms at the root of E2 action in cancer progression. Remarkably, several natural or synthetic exogenous chemicals, collectively called xenoestrogens, bind to ERs and interfere with their signals and intracellular functions. In this review, the molecular mechanism(s) through which xenoestrogens influence ERα and ERβ intracellular concentrations and the consequences of this influence on E2-related cancer will be discussed.
Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy.
Filippo
F
Acconcia
Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy.
Marco
M
Fiocchetti
Department of Sciences, Section Biomedical Sciences and Technology, University Roma Tre, Viale Guglielmo Marconi, 446, I-00146, Rome, Italy. Electronic address: maria.marino@uniroma3.it.
Maria
M
Marino
D000818:Animals; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008024:Ligands
17β-estradiol; Endocrine-related cancers; Estrogen receptors; Xenoestrogens