RT Journal Article
T1 Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines
A1 Rodríguez, Teresa
A1 Méndez, Rosa
A1 Campo, Ana Del
A1 Jiménez, Pilar
A1 Aptsiauri, Natalia
A1 Garrido, Federico
A1 Ruiz-Cabello, Francisco
K1 HLA Antigens
K1 IRF1 protein, human
K1 Interferon Regulatory Factor-1
K1 STAT1 Transcription Factor
K1 STAT1 protein, human
K1 Interferon-gamma
K1 Interferón gamma
K1 Melanoma
K1 Fosforilación Oxidativa
K1 Factor de Transcripción STAT1
K1 Transducción de Señal
K1 Neoplasias Cutáneas
K1 Activación Transcripcional
K1 Células Tumorales Cultivadas
K1 Antineoplastic Agents
AB BACKGROUNDThe inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-gamma-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-gamma treatment in human melanoma cell lines.METHODSBasal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan(R) Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-gamma-treated cells.RESULTSAltered IFN-gamma mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-alpha led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-gamma treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-alpha treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-gamma in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-gamma signaling pathway.CONCLUSIONWe observed two distinct mechanisms of loss of IFN-gamma inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-gamma signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence of IFN-gamma-mediated HLA class I expression in ESTDAB-159 cells is due to epigenetic blocking of IFN-regulatory factor 1 (IRF-1) transactivation.
PB BioMed Central
YR 2007
FD 2007-02-23
LK http://hdl.handle.net/10668/616
UL http://hdl.handle.net/10668/616
LA en
NO Rodríguez T, Méndez R, Campo A Del, Jiménez P, Aptsiauri N, Garrido, et al. Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines.BMC Cancer. 2007 Feb 23;7:34.
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025