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.