APOPTOSIS-INDEPENDENT RETINOBLASTOMA PROTEIN RESCUE OF HLA CLASS-II MESSENGER-RNA IFN-GAMMA INDUCIBILITY IN NON-SMALL-CELL LUNG-CARCINOMA CELLS - LACK OF SURFACE CLASS-II EXPRESSION ASSOCIATED WITH A SPECIFIC DEFECT IN HLA-DRA INDUCTION

Work from our laboratory indicates that HLA class II induction by IFN- gamma in the retinoblastoma (RB) protein-defective breast carcinoma li ne MDA-468-S4 (S4) requires reconstitution of functional RB. To determ ine whether RB is required for HLA class II expression in multiple tum or types, the RB-defective non-small cell lung carcinoma line H2009 an d its RB-reconstituted subclones were examined for class II inducibili ty, Surface HLA-DR (DR) was not inducible by IFN-gamma in H2009. Howev er, unlike the RB RB-reconstituted subclones of S4, DR surface express ion was not detected in the H2009 RB-positive subclones, IFN-gamma ind uction of CIITA, a major regulator of class II transcription, suggeste d that H2009 retained at least part of the IFN-gamma signaling pathway leading to class II expression. Examination of class II mRNA indicate d that IFN-gamma induction of DRB was rescued in the RB-positive subcl ones of H2009, confirming the requirement for RB for HLA class II indu cibility and revealing that RB is required for inducibility in develop mentally distinct tumor types, However, DRA inducibility was not rescu ed in the H2009 RB-positive subclones, which explained the lack of sur face DB induction in the RB-positive H2009 subclones, DPA and DPB were also only weakly inducible in the RB-reconstituted H2009 subclones, c ompared with the previously described, S4 RB-positive subclones, Final ly, data reported here indicates that RB's ability to inhibit IFN-gamm a-induced apoptosis is not a viable explanation for why RB expression rescues DRB inducibility in H2009.