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Evidences that estrogen receptor ? interferes with adiponectin effects on breast cancer cell growth
| Content Provider | Scilit |
|---|---|
| Author | Mauro, Loredana Pellegrino, Michele Amicis, Francesca De Ricchio, Emilia Giordano, Francesca Rizza, Pietro Catalano, Stefania Bonofiglio, Daniela Sisci, Diego Panno, Maria Luisa Andò, Sebastiano |
| Copyright Year | 2013 |
| Description | Journal: Cell Cycle 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. |
| Related Links | http://www.tandfonline.com/doi/pdf/10.4161/cc.27455?needAccess=true |
| Ending Page | 564 |
| Page Count | 12 |
| Starting Page | 553 |
| ISSN | 15384101 |
| e-ISSN | 15514005 |
| DOI | 10.4161/cc.27455 |
| Journal | Cell Cycle |
| Issue Number | 4 |
| Volume Number | 13 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2013-12-12 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cell Cycle Biochemistry and Molecular Biology Breast Cancer Cell Proliferation Estrogen Receptor Alpha |
| Content Type | Text |
| Subject | Cell Biology Developmental Biology Medicine Molecular Biology |
