PMID- 17608862 OWN - NLM STAT- MEDLINE DCOM- 20071003 LR - 20101118 IS - 0815-9319 (Print) IS - 0815-9319 (Linking) VI - 22 IP - 7 DP - 2007 Jul TI - Low-molecular-weight protein (LMP)2/LMP7 abnormality underlies the downregulation of human leukocyte antigen class I antigen in a hepatocellular carcinoma cell line. PG - 1155-61 AB - BACKGROUND: Tumor cells may alter the expression of numerous components involved in antigen-processing machinery to decrease human leukocyte antigen (HLA) class I expression, allowing the tumor cells to escape immune surveillance. The purpose of the present study was to investigate the involvement of these components in the downregulation of HLA class I expression in human hepatocellular carcinoma cell line BEL7,404. METHODS: Expression of HLA-I and antigen presentation-related genes were analyzed by flow cytometry and polymerase chain reaction. The HLA class I-deficient BEL7,404 cell was transfected with the low-molecular-weight protein (LMP) 2 and LMP7 gene and were analyzed by flow cytometry for restoration of surface HLA class I expression. RESULTS: The BEL7,404 cells downregulated the expression of HLA class I antigen and lacked expression of LMP2 and LMP7. Interferon (IFN)-gamma treatment increased the expression of LMP2 but not LMP7. The LMP2-transfected BEL7,404 cells or LMP2 and LMP7-cotransfected cells restored surface HLA class I expression while LMP7-transfected cells did not. However, in IFN-gamma-treated BEL7,404 cells, transfection with the LMP7 gene induced more HLA class I expression than mock transfection. CONCLUSIONS: The LMP2 gene was required for the expression of HLA class I molecules in BEL7,404. The LMP7 was not the major reason for loss of HLA class I in BEL7,404 cells, although the supply of exogenous LMP7 could increase surface expression of HLA class I antigen. FAU - Shen, Yu-Qing AU - Shen YQ AD - State Education Ministry Laboratory of Developmental Genes and Human Diseases, Jiangsu Provincial Key Laboratory of Gene Diagnosis and Therapy, Genetics Research Center, Southeast University Medical School, Nanjing, Jiangsu Province, China. FAU - Zhang, Jian-Qiong AU - Zhang JQ FAU - Xia, Mei AU - Xia M FAU - Miao, Feng-Qing AU - Miao FQ FAU - Shan, Xiang-Nian AU - Shan XN FAU - Xie, Wei AU - Xie W LA - eng GR - TW005900-01A2/TW/FIC NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Multienzyme Complexes) RN - 144416-78-4 (LMP-2 protein) RN - EC 3.4.22.- (Cysteine Endopeptidases) RN - EC 3.4.25.1 (LMP7 protein) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM MH - Carcinoma, Hepatocellular/*immunology MH - Cell Line, Tumor MH - Cysteine Endopeptidases/*physiology MH - *Down-Regulation MH - Histocompatibility Antigens Class I/*physiology MH - Humans MH - Leukocytes/*immunology MH - Liver Neoplasms/*immunology MH - Multienzyme Complexes/*physiology MH - Proteasome Endopeptidase Complex EDAT- 2007/07/05 09:00 MHDA- 2007/10/04 09:00 CRDT- 2007/07/05 09:00 PHST- 2007/07/05 09:00 [pubmed] PHST- 2007/10/04 09:00 [medline] PHST- 2007/07/05 09:00 [entrez] AID - JGH4421 [pii] AID - 10.1111/j.1440-1746.2006.04421.x [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2007 Jul;22(7):1155-61. doi: 10.1111/j.1440-1746.2006.04421.x.