title: Hypoxia inducible factor (HIF)-1α directly activates leptin receptor (Ob-R) in pancreatic cancer cells.
abstract: The aim of this study is to investigate the regulatory mechanism of leptin receptors (Ob-R) in pancreatic cancer. We found that the over-expression of hypoxia inducible factor (HIF-1)α and hypoxia up-regulated the expression of Ob-R in pancreatic cancer cells. When HIF-1α gene was silenced in vitro, the expression of Ob-R was significantly decreased. Xenograft mouse models showed that the inhibition of HIF-1α resulted in the concomitant decrease of Ob-R in vivo. In addition, HIF-1α expression was correlated with Ob-R in pancreatic cancer tissues by immunohistochemical staining. Clinical data showed that over-expression of HIF-1 was associated with pathological tumor node metastasis stage, lymph node metastasis and overall survival. HIF-1α directly bound to the hypoxia-responsive element (HRE) located in Ob-R gene promoter (-828/-832) and activated the transcription. Finally, we demonstrated that the silence of HIF-1α gene reversed the inhibitory effect of leptin/Ob-R in pancreatic cancer cells. Taken together, our results indicate that HIF-1α directly regulated Ob-R expression in pancreatic cancer, which might be a valuable therapeutic target for pancreatic cancer.
authors.affiliation: National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.affiliation: School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Jia
authors.affiliation: National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Tiansuo
authors.initials: T
authors.lastname: Zhao
authors.affiliation: National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Yang
authors.affiliation: National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.affiliation: National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Electronic address: haojihui@tjmuch.com.
authors.forename: Jihui
authors.initials: J
authors.lastname: Hao
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004338:Drug Combinations; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering; D054411:Receptors, Leptin; C059485:matrigel; D003094:Collagen
keywords: Hypoxia inducible factor-1α (HIF-1α); Leptin; Leptin receptor (Ob-R); Pancreatic cancer