title: Overexpression of human β-defensin 2 promotes growth and invasion during esophageal carcinogenesis.
abstract: Human β-defensin 2 (HBD-2) is an antimicrobial peptide produced by mucosal surfaces in response to microbial exposure or inflammatory cytokines. Although HBD-2 is expressed in the esophagus in response to stress and infectious agents, little is known regarding its expression and functional role in esophageal carcinogenesis. In the current investigation, normal esophagus and N-nitrosomethylbenzylamine (NMBA)-induced precancerous and papillomatous lesions of the rat esophagus were characterized for HBD-2 encoding gene Defb4 and protein. HBD-2 was found to be overexpressed in esophagi of rats treated with NMBA compared to animals in control group. Results of Real-time PCR, Western blot and immunohistochemistry demonstrated a positive correlation between the overexpression of HBD-2 and the progression of rat squamous cell carcinogenesis (SCC) in the esophagus. We also observed that HBD-2 is overexpressed in tumor tissues removed from patients with esophageal SCC. Moreover, Defb4 silencing in vitro suppresses the tumor cell proliferation, mobility and invasion in esophageal SCC cell line KYSE-150. The results from this study provide experimental evidence that HBD-2 may play an oncogenic role in the initiation and progression of esophageal SCC and thus serves as a target for chemopreventive and therapeutic interventions.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Ni
authors.initials: N
authors.lastname: Shi
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.affiliation: Center for Biostatistics, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, Ohio.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014162:Transfection; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C106641:DEFB4A protein, human; D012333:RNA, Messenger; D023083:beta-Defensins; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine