title: Expression of icb-1 gene is interferon-gamma inducible in breast and ovarian cancer cell lines and affects the IFN gamma-response of SK-OV-3 ovarian cancer cells.
abstract: Icb-1 (C1orf38) is a human gene initially described to be involved in in vitro differentiation processes of endometrial adenocarcinoma and leukemia cells. In this study, we examined the effect of interferon-gamma on icb-1alpha and beta mRNA levels in human cell lines derived from breast cancer and gynecological malignancies. Furthermore, we intended to approach icb-1 gene function by means of RNA interference (RNAi) to analyze the effect of an icb-1 knockdown on human cancer cells in vitro. Three breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231), three ovarian cancer cell lines (SK-OV-3, OVCAR-3 and BG-1) and the endometrial adenocarcinoma cell line HEC-1-A were treated with interferon gamma and the transcript levels of icb-1 isoforms alpha and beta were assessed by means of semiquantitative real-time RT-PCR. Our data demonstrates an interferon-gamma triggered upregulation of icb-1alpha mRNA levels in all breast cancer cell lines and an increase of icb-1beta mRNA in MDA-MB-231 cells. The strongest (about 10-fold) increase of icb-1alpha and beta mRNA after treatment with interferon-gamma was observed in ovarian cancer cell line SK-OV-3. Additionally, our data demonstrates the success of a siRNA-mediated knockdown of icb-1alpha and beta mRNA levels, which resulted in a significant increase of the antiproliferative interferon-gamma effect on SK-OV-3 cells. In conclusion, we report identification of the novel interferon-gamma inducible gene icb-1 which is able to affect the response of ovarian cancer cells to this cytokine.
authors.affiliation: Department of Obstetrics and Gynecology, University of Regensburg, Caritas Krankenhaus St. Josef, Landshuter Str. 65, 93053 Regensburg, Germany. otreeck@caritasstjosef.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Treeck
authors.forename: Ina
authors.initials: I
authors.lastname: Kindzorra
authors.forename: Katharina
authors.initials: K
authors.lastname: Pauser
authors.forename: Linda
authors.initials: L
authors.lastname: Treeck
authors.forename: Olaf
authors.initials: O
authors.lastname: Ortmann
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C111850:THEMIS2 protein, human; D007371:Interferon-gamma