Xia M, Zhang J Q, Shen Y-Q, Xu L H, Chen A Q, Miao F Q, Xie W
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.
Tissue Antigens. 2007 Oct;70(4):272-82. doi: 10.1111/j.1399-0039.2007.00892.x.
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.
许多恶性癌细胞下调人类白细胞抗原（HLA）I类抗原表达以逃避T细胞识别。然而，肝细胞癌（HCC）与癌细胞的一般情况不同，其上调机制尚不清楚。据报道，早幼粒细胞白血病（PML）原癌基因控制小鼠癌细胞中多个I类抗原呈递基因的转录。为了探究PML基因在HCC细胞中HLA I类抗原表达增加方面的功能作用，我们分析了在中国获取的HCC标本中原癌基因PML和多个I类抗原呈递基因的表达。结果显示，在44个石蜡包埋的HCC组织中原癌基因PML和细胞表面HLA - A表达呈现一致变化。此外，通过逆转录聚合酶链反应（RT - PCR）在15个新鲜HCC组织中的9个中检测到PML基因和I类抗原呈递基因的共同上调表达。另外，使用HCC细胞系的研究表明，通过RT - PCR、蛋白质印迹法和流式细胞术在QGY - 7701 HCC细胞系中检测到HLA I类分子表达增加与PML上调平行，并且在低表达I类细胞系BEL - 7405中外源PML的过表达可诱导多个I类抗原呈递分子基因的表达，并轻微但显著增加细胞表面HLA I类分子的表达。总之，原癌基因PML和HLA I类分子的表达一致上调，PML基因的表达可能是导致HCC中I类抗原表达增加的机制之一。
