title: EBP1 protein modulates the expression of human MHC class II molecules in non-hematopoietic cancer cells.
abstract: Many solid tumours including melanoma, glioblastoma, and breast carcinomas express MHC class II molecules (MHC II). The surface expression of these molecules confers to non-hematopoietic tumour cells the role of non-professional antigen presenting cells and the ability to potentially stimulate tumour-specific CD4+ T cell response. We studied EBP1, an ErbB3 binding protein, and the effects of p48 and p42 isoforms on the MHC II expression in U87 glioblastoma, M14 melanoma and MCF7 mammary carcinoma cell lines. We found that overexpression of p48 increases MHC II transcription in U87 and M14, through upregulation of CIITA transactivator and STAT1 phosphorylation. In addition, p48 protein influences MHC II expression by increasing mRNA stability. In melanoma and glioblastoma cell lines, p48 isoform functions as oncogene promoting tumour growth, while p42 isoform, that does not affect MHC II expression, acts as a tumour suppressor by blocking cell growth and inducing apoptosis. In contrast, p48 seems to act as tumour suppressor in breast carcinoma inhibiting proliferation, favouring apoptosis, and inducing a slight increase of MHC II expression similar to p42. Our data highlight the tissue specificity function of EBP1 isoforms and demonstrate that only the oncogene p48 activates MHC II expression in human solid tumours, via STAT1 phosphorylation, in order to affect tumour progression by triggering specific immune response.
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati Traverso'-CNR, 80131 Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pisapia
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati Traverso'-CNR, 80131 Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Barba
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati Traverso'-CNR, 80131 Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Cortese
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati Traverso'-CNR, 80131 Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cicatiello
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati Traverso'-CNR, 80131 Naples, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Morelli
authors.affiliation: Institute of Genetics and Biophysics 'Adriano Buzzati Traverso'-CNR, 80131 Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Pozzo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005802:Genes, MHC Class II; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101633:PA2G4 protein, human; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human