title: HER2 induces expression of leptin in human breast epithelial cells.
abstract: A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ∼30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy.  [BMB Reports 2012; 45(12): 719-723].
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 132-714, Korea.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Cha
authors.forename: Youjin
authors.initials: Y
authors.lastname: Kang
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
mesh_terms: D001940:Breast / Q000166:cytology* / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020738:Leptin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases