title: Evidences that estrogen receptor α interferes with adiponectin effects on breast cancer cell growth.
abstract: Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, anti-inflammatory, antiatherogenic, and antiproliferative properties. In addition, it appears to play an important role also in the development and progression of several obesity-related malignancies, including breast cancer.   Here, we demonstrated that adiponectin induces a dichotomic effect on breast cancer growth. Indeed, it stimulates growth in ERα+ MCF-7 cells while inhibiting proliferation of ERα- MDA-MB-231 cells. Notably, only in MCF-7 cells adiponectin exposure exerts a rapid activation of MAPK phosphorylation, which is markedly reduced when knockdown of the ERα gene occurred. In addition, adiponectin induces rapid IGF-IR phosphorylation in MCF-7 cells, and the use of ERα siRNA prevents this effect. Moreover, MAPK activation induced by adiponectin was reversed by IGF-IR siRNA. Coimmunoprecipitation studies show the existence of a multiprotein complex involving AdipoR1, APPL1, ERα, IGF-IR, and c-Src that is responsible for MAPK signaling activation in ERα+ positive breast cancer cells. It is well known that in addition to the rapid effects through non-genomic mechanisms, ERα also mediates nuclear genomic actions. In this concern, we demonstrated that adiponectin is able to transactivate ERα in MCF-7 cells. We showed the classical features of ERα transactivation: nuclear localization, downregulation of mRNA and protein levels, and upregulation of estrogen-dependent genes. Thus, our study clarifies the molecular mechanism through which adiponectin modulates breast cancer cell growth, providing evidences on the cell-type dependency of adiponectin action in relationship to ERα status.
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy.
authors: Loredana
authors: L
authors: Mauro
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy.
authors: Michele
authors: M
authors: Pellegrino
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy.
authors: Francesca
authors: F
authors: De Amicis
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy.
authors: Emilia
authors: E
authors: Ricchio
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy.
authors: Francesca
authors: F
authors: Giordano
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy.
authors: Pietro
authors: P
authors: Rizza
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy.
authors: Stefania
authors: S
authors: Catalano
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy.
authors: Daniela
authors: D
authors: Bonofiglio
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy.
authors: Diego
authors: D
authors: Sisci
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy.
authors: Maria Luisa
authors: ML
authors: Panno
authors: Department of Pharmacy, Health, and Nutritional Sciences; University of Calabria; Cosenza, Italy; Centro Sanitario; University of Calabria; Cosenza, Italy.
authors: Sebastiano
authors: S
authors: Andò
mesh_terms: D052242:Adiponectin / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D015533:Transcriptional Activation
chemical_list: D052242:Adiponectin; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha
keywords: APPL1; AdipoR1; IGF-IR; MAPK; adiponectin; breast cancer; cell proliferation; estrogen receptor alpha