title: Insulin-like growth factor-2 (IGF-2) activates estrogen receptor-α and -β via the IGF-1 and the insulin receptors in breast cancer cells.
abstract: The estrogen receptor (ER) is a primary target for breast cancer (BC) treatment. As BC progresses to estrogen-independent growth, the insulin-like growth factor-1 receptor (IGF-1R) and the ER interact in synergistic cross-talk mechanisms, which result in enhanced activation of both receptors' signaling cascades. Insulin-like growth factor-2 (IGF-2) is critical in BC progression and its actions are mediated by the IGF-1R. Our previous studies showed that IGF-2 regulates survival genes that protect the mitochondria and promote chemoresistance. In this study, we analyzed BC cells by subcellular fractionation, Western-Blot, qRT-PCR, and siRNA analysis. Our results demonstrate that IGF-2 activates ER-α and ER-β, and modulates their translocation to the nucleus, membrane organelles, and the mitochondria. IGF-2 actions are mediated by the IGF-1R and the insulin receptor. This novel mechanism of IGF-2 synergistic cross-talk signaling with ER-α and ER-β can promote estrogen-independent BC progression and provide new therapeutic targets for the treatment of BC patients.
authors.affiliation: School of Medicine, Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Richardson
authors.forename: N
authors.initials: N
authors.lastname: Hamilton
authors.forename: W
authors.initials: W
authors.lastname: Davis
authors.forename: C
authors.initials: C
authors.lastname: Brito
authors.forename: D
authors.initials: D
authors.lastname: De León
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin