title: Dysregulation of overexpressed IL-32α in hepatocellular carcinoma suppresses cell growth and induces apoptosis through inactivation of NF-κB and Bcl-2.
abstract: IL-32 is a newly discovered cytokine. Recently, various reports suggest that it plays a role as a proinflammatory mediator and may be involved in several cancer carcinogenesis. However, IL-32 expression in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression and role of IL-32α in hepatocellular carcinoma, because IL-32 was identified as an upregulated gene in hepatocellular carcinoma tissues compared to nontumorous regions using DNA microarray. IL-32α was overexpressed in tissue and serum from patients with HCC and localized in the cytoplasm and nucleus of hepatocellular carcinoma tumor cells. Moreover, secreted IL-32α concentration in the serum of patients with hepatocellular carcinoma was elevated as compared with those in the normal serum using a developed sandwich ELISA. Furthermore, IL-32α suppression in hepatocellular carcinoma decreased expression of phospho-p38 MAPK, NF-κB, and antiapoptotic protein Bcl-2 and induced expression of proapoptotic proteins as well as p53 and PUMA resulting in the suppression of cell growth and induction of intrinsic apoptosis. Based on our results, we suggest that IL-32α is involved in the progression of hepatocellular carcinoma and may be a useful biomarker for diagnosis and therapeutic target of hepatocellular carcinoma.
authors.affiliation: Medical Genomics Research Center, Daejeon, Republic of Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kang
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Park
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Seung Ro
authors.initials: SR
authors.lastname: Han
authors.forename: Chung Il
authors.initials: CI
authors.lastname: Lee
authors.forename: Na Young
authors.initials: NY
authors.lastname: Ji
authors.forename: Pyung-Keun
authors.initials: PK
authors.lastname: Myung
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yeom
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Dong Kuk
authors.initials: DK
authors.lastname: Ahn
authors.forename: Jong Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Song
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood / Q000502:physiology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000097:blood / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; C496971:IL32 protein, human; D007378:Interleukins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2