Gene expression profiles in human mesothelioma cell lines in response to interferon-gamma treatment.
Interferon-gamma (IFN-gamma) has been found to be antiproliferative and antitumoral in malignant mesothelioma (MM), but the MM cell response to IFN-gamma has not been fully characterized so far. We investigated gene expression profiles in human MM cell lines (HMCLs) exposed to IFN-gamma. Four HMCLs showing different sensitivities to the antiproliferative effect of IFN-gamma, two of them presenting a defect in the JAK/STAT signaling pathway, were treated with 500 IU/mL of IFN-gamma. Gene expression patterns were studied at 6 and 72 hours after exposure to the IFN-gamma, using a cDNA array technique. Six genes were studied with real-time reverse transcription-polymerase chain reaction. The gene expression profiles in response to IFN-gamma were shown to differ in different HMCLs. Numerous genes involved in cell proliferation and cell adhesion were regulated by IFN-gamma in JAK/STAT-deficient HMCLs. Genes possibly involved in regulation of cell proliferation included CDC2, PLK1, and IGFBP4, as well as several genes involved in cell-cell interactions and cell adhesion. The cDNA array technique revealed differences in expression pathways, especially those involved in cell growth, cell adhesion, and cell proliferation, between IFN-gamma-resistant and -sensitive MM cell lines. We found that the changes in gene expression profiles of HMCLs exposed to IFN-gamma were also related to features other than the antiproliferative response.
Kettunen
Eeva
E
Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki, Finland.
Vivo
Claire
C
Gattacceca
Florence
F
Knuutila
Sakari
S
Jaurand
Marie-Claude
MC
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007371:Interferon-gamma