title: Interferon alfa receptor expression and growth inhibition by interferon alfa in human liver cancer cell lines.
abstract: Type I interferon (IFN) receptor consists of two chains (Hu-IFN-alphaR1 and Hu-IFN-alphaR2), and Hu-IFN-alphaR2 takes a soluble (Hu-IFN-alphaR2a), short (Hu-IFN-alphaR2b), or long (Hu-IFN-alphaR2c) form. We examined the expression of type I IFN receptor, the growth-suppression effect of IFN-alpha, and their relationship in 13 liver cancer cell lines. With reverse-transcription polymerase chain reaction (RT-PCR) analysis, the expressions of Hu-IFN-alphaR1, Hu-IFN-alphaR2a, and Hu-IFN-alphaR2c were confirmed in all cell lines, and that of Hu-IFN-alphaR2b in 12 cell lines. All cell lines expressed mRNAs of a transcriptional activator, interferon regulatory factor (IRF)-1, and its antagonistic repressor (IRF-2). Flow cytometry revealed weak expression of Hu-IFN-alphaR2 on the cell surface in 12 cell lines. The soluble-form protein of Hu-IFN-alphaR2 was detected at varying levels in culture supernatants of all cell lines with enzyme-linked immunosorbent assay (ELISA). Cell proliferation was suppressed in proportion to the dose of human natural IFN-alpha at 96 hours of culture, but it was not clearly related to the expression of Hu-IFN-alphaR2 protein on the cell surface. Investigations on the morphology, DNA, and cell cycle presented four growth suppression patterns as a result of IFN-alpha: 1) induction of apoptosis and blockage of cell cycle at the S phase (9 cell lines); 2) blockage at the S phase (2 cell lines); 3) induction of apoptosis and blockage at the G2/M phase (1 cell line); and 4) blockage at the G1 phase (1 cell line). There was no evidence showing that changes in the expressions of Bcl-2, Bcl-xL, Bak, and Bax lead directly to IFN-alpha-mediated apoptosis. Our findings demonstrated that IFN-alpha would express growth-suppression effects at varying degrees by inducing inhibition of cell-cycle progression with or without apoptosis, regardless of the expression level of Hu-IFN-alphaR2 protein on the cell surface.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan. hiroyano@med.kurome-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Yano
authors.forename: A
authors.initials: A
authors.lastname: Iemura
authors.forename: M
authors.initials: M
authors.lastname: Haramaki
authors.forename: S
authors.initials: S
authors.lastname: Ogasawara
authors.forename: A
authors.initials: A
authors.lastname: Takayama
authors.forename: J
authors.initials: J
authors.lastname: Akiba
authors.forename: M
authors.initials: M
authors.lastname: Kojiro
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D008113:Liver Neoplasms / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D016898:Interferon-alpha; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta