title: Concordant expression of proto-oncogene promyelocytic leukemia and major histocompatibility antigen HLA class I in human hepatocellular carcinoma.
abstract: Many malignant cancer cells downregulate human leukocyte antigen (HLA) class I antigen expression to evade T cell recognition. However, hepatocellular carcinoma (HCC) is exceptional to the general findings in cancer cells, and the mechanisms for its upregulation remain unclear. It has been reported that promyelocytic leukemia (PML) proto-oncogene controls the transcription of multiple class I antigen presentation genes in murine cancer cells. To find out the functional role of PML gene on the increased HLA class I antigen expression in HCC cells, we analyzed the expression of proto-oncogene PML and multiple class I antigen presentation genes in HCC specimens obtained in China. The results showed concordant changes of proto-oncogene PML and cell surface HLA-A expression in 44 paraffin-embedded HCC tissues. Furthermore, co-upregulated expression of PML genes and class I antigen presentation genes could be detected in 9 of 15 fresh HCC tissues by reverse transcription polymerase chain reaction (RT-PCR). In addition, studies using HCC cell lines showed that increased expression of HLA class I molecules paralleled with PML upregulation were detected in QGY-7701 HCC cell line with RT-PCR, western blot, and flow cytometry, and that the overexpression of exogenous PML in a low-expression class I cell line BEL-7405 could induce the expression of multiple class I antigen-presenting molecule genes and slightly but significantly increase the expression of cell surface HLA class I molecules. In conclusion, the expression of proto-oncogene PML and HLA class I molecules were concordantly upregulated and the expression of PML gene might be one of the mechanisms that leads to the increased expression of class I antigen in HCC.
authors.affiliation: Key Laboratory of the Education Ministry of China for Developmental Genes and Human Diseases, Southeast University Medical School, 87 Dingjiaqiao Road, Nanjing 210009, Jiangsu, China.
authors.forename: M
authors.initials: M
authors.lastname: Xia
authors.forename: J Q
authors.initials: JQ
authors.lastname: Zhang
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Shen
authors.forename: L H
authors.initials: LH
authors.lastname: Xu
authors.forename: A Q
authors.initials: AQ
authors.lastname: Chen
authors.forename: F Q
authors.initials: FQ
authors.lastname: Miao
authors.forename: W
authors.initials: W
authors.lastname: Xie
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002681:China; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015395:Histocompatibility Antigens Class I; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human