Hypoxic induction of human visfatin gene is directly mediated by hypoxia-inducible factor-1.
Visfatin has been originally identified as a growth factor for early stage B cells and recently known as an adipokine. Here, we report that hypoxia induces the visfatin mRNA and protein levels in MCF7 breast cancer cells. We also demonstrate that induction of visfatin gene is regulated by hypoxia-inducible factor-1alpha (HIF-1alpha). Moreover, 5'-flanking promoter region of human visfatin gene contains two functional HIF responsive elements (HREs), activating the expression of visfatin. Mutation of these HREs in the visfatin promoter abrogates activation of a luciferase reporter gene driven by visfatin promoter under hypoxia. Taken together, our results demonstrate that visfatin is a new hypoxia-inducible gene of which expression is stimulated through the interaction of HIF-1 with HRE sites in its promoter region.
Bae
Soo-Kyung
SK
College of Dentistry and Research Institute for Oral Biotechnology, Pusan National University, Pusan 602-739, South Korea.
Kim
Su-Ryun
SR
Kim
Jong Gab
JG
Kim
Jee Yeon
JY
Koo
Tae Hyeon
TH
Jang
Hye-Ock
HO
Yun
Il
I
Yoo
Mi-Ae
MA
Bae
Moon-Kyoung
MK
D001402:B-Lymphocytes / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009154:Mutation; D054409:Nicotinamide Phosphoribosyltransferase; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020218:Response Elements / Q000502:physiology*
D016207:Cytokines; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human