title: The role of leptin in gastric cancer: clinicopathologic features and molecular mechanisms.
abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n=38), early gastric cancer (EGC) (n=38), and advanced gastric cancer (AGC) (n=38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Kang Nyeong
authors.initials: KN
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea. Electronic address: hschoi96@hanyang.ac.kr.
authors.forename: Ho Soon
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Hyun Ki
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Young Yiul
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Joon Soo
authors.initials: JS
authors.lastname: Hahm
authors.affiliation: Pathology, Hanyang University College of Medicine, Seoul, South Korea.
authors.forename: Seung Sam
authors.initials: SS
authors.lastname: Paik
mesh_terms: D000236:Adenoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000032:analysis* / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D054411:Receptors, Leptin / Q000032:analysis / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A
keywords: ERK1/2; Gastric cancer; Leptin; Leptin receptor; STAT3