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Retinoids and interferons are signaling molecules with pronounced anticancer activity. We show that in both acute promyelocytic leukemia and breast cancer cells the retinoic acid (RA) and interferon signaling pathways converge on the promoter of the tumoricidal death ligand TRAIL. Promoter mapping, chromatin immunoprecipitation and RNA interference reveal that retinoid-induced interferon regulatory factor-1 (IRF-1), a tumor suppressor, is critically required for TRAIL induction by both RA and IFN?. Exposure of breast cancer cells to both antitumor agents results in enhanced TRAIL promoter occupancy by IRF-1 and coactivator recruitment, leading to strong histone acetylation and synergistic induction of TRAIL expression. In coculture experiments, pre-exposure of breast cancer cells to RA and IFN? induced a dramatic TRAIL-dependent apoptosis in heterologous cancer cells in a paracrine mode of action, while normal cells were not affected. Our results identify a novel TRAIL-mediated tumor suppressor activity of IRF-1 and suggest a mechanistic basis for the synergistic antitumor activities of certain retinoids and interferons. These data argue for combination therapies that activate the TRAIL pathway to eradicate tumor cells. [ABSTRACT FROM AUTHOR]

Employer offerings of on-site child care benefits have grown tremendously in the past few decades; both beneficial and detrimental effects on worker attitudes and behaviors have been noted. Some research suggests that offering on-site child care benefits can cause resentment among childless workers and/or workers with children who do not use the center. In a field sample of 271 employees, current and past use of the on-site child care center, as well as anticipated future use of the on-site child care center, were related to more positive proximal reactions such as attitudes closely related to the on-site child care center, but not to more general attitudes or behaviors. Results indicate that any ‘family-friendly backlash’ may be limited to proximal reactions. These findings are discussed in light of organizational justice theories. [ABSTRACT FROM AUTHOR]