Cytokine induced apoptosis in human retinoblastoma cells.

PURPOSE To determine potential anti-proliferative properties of interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF-alpha) on human retinoblastoma cells. METHODS Fluorescent antibody staining was used to detect IFN-gamma and TNF-alpha receptors on the cells. Y79 and Weri Rb-1 cells were exposed to IFN-gamma alone, TNF-alpha alone, or a combination of IFN-gamma and TNF-alpha, and apoptosis was measured by caspase 3 activation and annexin V staining. Cell cycle arrest was measured by BrdU incorporation and FACS analysis. RESULTS Both cell lines expressed receptors for IFN-gamma and TNF-alpha. There appeared to be two populations of both receptors in the Weri Rb-1 cell line. Apoptosis was induced in Y79 cells by IFN-gamma, but not TNF-alpha, and the combination of the cytokines did not increase apoptosis above IFN-gamma alone in Y79 cells. Apoptosis was induced in Weri Rb-1 cells only upon exposure to both cytokines. The cell cycle was not significantly altered in either cell line. CONCLUSIONS Human retinoblastoma cells respond to IFN-gamma or a combination of IFN-gamma and TNF-alpha by becoming apoptotic, but Y79 and Weri Rb-1 cells behave differently. The differential response of the two cell lines is not due to a lack of expression of IFN-gamma or TNF-alpha receptors. The data raise the possibility that differences in apoptotic pathways exist between the two cell lines with interesting implications for the induction of apoptosis as a therapy for retinoblastoma.