Expression of icb-1 gene is interferon-gamma inducible in breast and ovarian cancer cell lines and affects the IFNγ-response of SK-OV-3 ovarian cancer cells

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-1α and β 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 α and β were assessed by means of semiquantitative real-time RT-PCR. Our data demonstrates an interferon-gamma triggered upregulation of icb-1α mRNA levels in all breast cancer cell lines and an increase of icb-1β mRNA in MDA-MB-231 cells. The strongest (about 10-fold) increase of icb-1α and β 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-1α and β 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.