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- W2316400913 abstract "We have previously reported that HLA class II induction by IFN‐γ is rescuable by reconstitution of functional retinoblastoma protein (RB) in two RB‐defective tumour lines: the breast carcinoma line. MDA‐ 468‐S4 (S4) and the non‐small cell lung carcinoma line. H2009. To determine the range of tumours and tumour types in which RB rescues HLA class II inducibility, we examined another RB‐defective tumour line. the retinoblastoma line. WERI‐Rb1. As in the case of S4 and H2009, HLA‐DRA and ‐DRB were non‐inducible by IFN‐γ in WERI‐Rb1. However, neither inducibility of DRA nor DRB mRNA was restored in an RB‐positive stable transformant of WERI‐Rb1. WLRB‐S, While guanylate‐binding protein (GBP) inducibility indicated that the basic IFN‐7 signal transduction pathway remained intact in WERI‐Rb1, mRNA for class II transactivator (CIITA), a mediator of the IFN‐γ activation of the HLA class II genes and several other genes related to immune function, was not detectable in IFN‐γ‐treated WERI‐Rbl. indicating that the lack of CIITA expression was responsible, at least in pan. for the inability of RB to rescue HLA class Il‐inducibility. The HLA class Il‐associated invariant chain (Ii), the expression of which is also up‐regulated by CIITA. was non‐inducible in WERI‐Rb1. consistent with non‐inducible CIITA. Also. IFN‐γ failed to activate the DRA. DRB and Ii promoters in WERI‐Rb1. However, exogenous CIITA expression in WERI‐Rb1 activated the DRA. DRB and Ii promoter‐chloramphinocol acetyltransferase constructs, confirming that CIITA was not induced in WERI‐Rb1 and indicating that other proteins required for activation of the class II and Ii promoters were functional in this cell lines. Examination of additional cell lines for GBP and CIITA induction revealed that a specific lack of the CIITA IFN‐γ response is common in human tumour lines. The possible role of CIITA defects in tumorigenesis is discussed." @default.
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- W2316400913 date "1997-08-01" @default.
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- W2316400913 title "IFN-γ inducibility of class II transactivator is specifically lacking in human tumour lines: Relevance to retinoblastoma protein rescue of IFN-γ inducibility of the HLA class II genes" @default.
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- W2316400913 doi "https://doi.org/10.1038/icb.1997.50" @default.
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