title: Estrogen receptor-α drives adiponectin effects on cyclin D1 expression in breast cancer cells.
abstract: Obesity is a risk factor for breast cancer, largely due to altered expression of various adipocytokines. As it concerns adiponectin, there are not univocal results regarding its role in breast cancer occurrence and progression. Here, we demonstrate that in animals injected with human estrogen receptor (ER)-α-negative MDA-MB-231 cells pretreated with adiponectin (1 and 5 µg/ml), a significant reduction (60 and 40%, respectively) in tumor volume is observed, whereas an increased tumor growth (54 and 109%, respectively) is evidenced in the animals receiving human ER-α-positive MCF-7 cells. Moreover, cyclin D1 (CD1) mRNA and protein levels are decreased in MDA-MB-231 cells, whereas they are up-regulated in ER-α-positive cells by adiponectin. These findings fit with the opposite effects of adiponectin on CD1 promoter: 0.44- and 0.34-fold decrease in MDA-MB-231 cells and 0.63- and 0.95-fold increase in MCF-7 cells, treated with 1 and 5 µg/ml, respectively. Functional studies indicate that these effects are mediated by the specific protein 1 motif located in the CD1 promoter. In the absence of ER-α, the adiponectin-mediated down-regulation of CD1 involves the recruitment of corepressors. In the presence of ER-α, the adiponectin-induced expression of CD1 requires the involvement of an activator complex. In conclusion, we propose that a possible mechanism through which adiponectin differently affects breast cancer growth is the opposite modulation of CD1 levels accordingly to ER-α expression.
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy doclollo@yahoo.com sebastiano.ando@unical.it.
authors: Loredana
authors: L
authors: Mauro
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Michele
authors: M
authors: Pellegrino
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Francesca
authors: F
authors: Giordano
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Emilia
authors: E
authors: Ricchio
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Pietro
authors: P
authors: Rizza
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Francesca
authors: F
authors: De Amicis
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Stefania
authors: S
authors: Catalano
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Daniela
authors: D
authors: Bonofiglio
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy.
authors: Maria Luisa
authors: ML
authors: Panno
authors: *Department of Pharmacy, Health and Nutritional Sciences, and Centro Sanitario, University of Calabria, Arcavacata di Rende, Italy doclollo@yahoo.com sebastiano.ando@unical.it.
authors: Sebastiano
authors: S
authors: Andò
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D052242:Adiponectin; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D019938:Cyclin D1
keywords: AMPK; MAPK; Sp1; corepressors; xenografts