title: Visfatin promotes cell and tumor growth by upregulating Notch1 in breast cancer.
abstract: Overexpression of Notch1 has been associated with breast cancer. We recently showed that visfatin stimulates breast cancer cell proliferation and invasion. The present study was undertaken to determine whether Notch1 signaling is affected by visfatin and to characterize the functional role of the visfatin-Notch1 axis in breast cancer. Visfatin and Notch1 were expressed at higher levels in breast tumors than in matched control tissues. Visfatin induced Notch1 expression in MDA-MB-231 breast cancer cell line and in nontransformed MCF10A mammary epithelial cells, whereas visfatin depletion reduced Notch1 mRNA and protein levels. Depletion of Notch1 in MDA-MB-231 cells attenuated cell growth in vitro and in vivo; visfatin depletion produced similar effects, but was less potent. Additionally, Notch1 depletion inhibited cell proliferation induced by visfatin. Analysis of the signaling pathways underlying visfatin-mediated Notch1 upregulation revealed that visfatin activated NF-κB p65. Blockade of NF-κB signaling suppressed the effects of visfatin on Notch1 upregulation and breast cancer cell proliferation. Breast tumors expressing high levels of NF-κB p65 exhibited increased expression of Notch1. Our results demonstrate that the visfatin-Notch1 axis contributes to breast tumor growth through the activation of the NF-κB pathway. Study of the visfatin-Notch1 axis may offer new therapeutic directions for breast cancer.
authors: Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors: Hyun-Joo
authors: HJ
authors: Park
authors: Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors: Su-Ryun
authors: SR
authors: Kim
authors: Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors: Su Seong
authors: SS
authors: Kim
authors: Department of Biochemistry, College of Pharmacy, Seoul National University, Seoul, South Korea.
authors: Hee-Jun
authors: HJ
authors: Wee
authors: Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors: Moon-Kyoung
authors: MK
authors: Bae
authors: Department of Oral Pathology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors: Mi Heon
authors: MH
authors: Ryu
authors: Department of Dental Pharmacology, School of Dentistry, Pusan National University, Yangsan, South Korea.
authors: Soo-Kyung
authors: SK
authors: Bae
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D008819:Mice, Nude; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism; D047368:Tumor Burden / Q000235:genetics; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D051881:Receptor, Notch1; D051996:Transcription Factor RelA; D054409:Nicotinamide Phosphoribosyltransferase