title: Network analysis of icb-1 gene function in human breast cancer cells.
abstract: Icb-1 is a human gene previously described by our group to exert important functions in cancer cells of different origin. We now performed microarray-based gene expression profiling with subsequent network modeling to further elucidate the role of icb-1 in breast cancer cells. Analyzing the effect of icb-1 knockdown on the transcriptome of MCF-7 cells, we found 151 differentially expressed genes exhibiting more than twofold changes, 97 of which were up- and 54 downregulated. Most of the upregulated genes were cancer-related genes associated with poor prognosis, invasion and metastasis, building an oncogenic network of TNF target genes. On the other hand, network analysis identified the downregulated genes to be primarily involved in interferon signaling and cellular apoptosis. Confirming these network data, we observed that cells with reduced levels of icb-1 exhibited an impaired response to the apoptosis inducers tamoxifen, staurosporine, actinomycin, and camptothecin. The data of this study suggest that icb-1 might exert a tumor-suppressor function in breast cancer and that its loss might confer relative resistance of breast cancer cells to apoptotic drugs.
authors.affiliation: Department of Obstetrics and Gynecology, Laboratory of Molecular Oncology, University Medical Center Regensburg, Regensburg, Germany. otreeck@caritasstjosef.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Treeck
authors.forename: Derya
authors.initials: D
authors.lastname: Belgutay
authors.forename: Julia
authors.initials: J
authors.lastname: Häring
authors.forename: Susanne
authors.initials: S
authors.lastname: Schüler
authors.forename: Claus
authors.initials: C
authors.lastname: Lattrich
authors.forename: Olaf
authors.initials: O
authors.lastname: Ortmann
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C111850:THEMIS2 protein, human