Cytokine induced apoptosis in human retinoblastoma cells.
OBJECTIVE
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.
Cullinan
Amy E
AE
Department of Medical Microbiology and Immunology, University of Wisconsin-Medical School, Madison, WI 53706, USA.
Brandt
Curtis R
CR
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D004261:DNA Replication; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D017471:Receptors, Interferon / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D019572:Retinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000096743:Interferon gamma Receptor
D017304:Annexin A5; D000970:Antineoplastic Agents; D053148:Caspase 3; D020169:Caspases; D007371:Interferon-gamma; D017471:Receptors, Interferon; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C505407:CASP3 protein, human