PMID- 19883394
OWN - NLM
STAT- MEDLINE
DCOM- 20100805
LR  - 20210103
IS  - 1399-0039 (Electronic)
IS  - 0001-2815 (Linking)
VI  - 75
IP  - 1
DP  - 2010 Jan
TI  - Hypermethylation of HLA class I gene is associated with HLA class I 
      down-regulation in human gastric cancer.
PG  - 30-9
LID - 10.1111/j.1399-0039.2009.01390.x [doi]
AB  - Down-regulated expression of human leukocyte antigen (HLA) class I molecules in 
      many human cancers facilitate tumor cells to escape from immune attack. Promoter 
      hypermethylation, one of the major epigenetic changes responsible for gene 
      inactivation, plays an important role in gastric carcinogenesis. This study 
      evaluated the expression and alteration of HLA class I molecules in a panel of 47 
      pairs of gastric cancer specimens with their noncancerous parts from Chinese 
      patients by using immunohistochemistry (IHC), reverse transcription polymerase 
      chain reaction (RT-PCR) and methylation-specific PCR (MSP) analysis. The 
      expression of HLA-A, HLA-B/C and HLA class I complex was lost or down-regulated 
      in human gastric cancer. The percentage of promoter methylation was 59.57% for 
      HLA-A gene, 55.32% for HLA-B gene and 48.94% for HLA-C gene in gastric cancer, 
      while it was decreased to 19.15%, 12.77% and 6.38% in the adjacent nontumor 
      tissues, respectively. Seven of 10 (70%), 4 of 6 (66.7%) and 3 of 4 (75%) gastric 
      cancer specimens with promoter hypermethylation at HLA-A, -B and -C loci showed 
      transcriptional inactivation of HLA-A,-B and -C genes, suggesting an association 
      between promoter hypermethylation and down-regulated expression of HLA class I 
      molecules. Human gastric cancer cell line BGC-823 showed HLA-A down-regulation 
      with promoter methylation of HLA-A locus. Treatment with DNA methyltransferase 
      inhibitor restored the expression of HLA-A mRNA and surface HLA-A complex. Thus, 
      our results showed that promoter hypermethylation might be one of the mechanisms 
      that lead to HLA class I antigen down-regulation in gastric cancer.
FAU - Ye, Q
AU  - Ye Q
AD  - Department of Genetics and Developmental Biology, The Key Laboratory of the 
      Ministry of Education of China for Developmental Genes and Human Disease, 
      Southeast University Medical School, Nanjing, Jiangsu Province, China.
FAU - Shen, Y
AU  - Shen Y
FAU - Wang, X
AU  - Wang X
FAU - Yang, J
AU  - Yang J
FAU - Miao, F
AU  - Miao F
FAU - Shen, C
AU  - Shen C
FAU - Zhang, J
AU  - Zhang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091030
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic
MH  - *DNA Methylation
MH  - Down-Regulation
MH  - Epigenesis, Genetic
MH  - *Genes, MHC Class I
MH  - HLA-A Antigens/*genetics/metabolism
MH  - HLA-B Antigens/genetics/metabolism
MH  - HLA-C Antigens/genetics/metabolism
MH  - Humans
MH  - Stomach Neoplasms/*genetics/metabolism
MH  - Transcription, Genetic
EDAT- 2009/11/04 06:00
MHDA- 2010/08/06 06:00
CRDT- 2009/11/04 06:00
PHST- 2009/11/04 06:00 [entrez]
PHST- 2009/11/04 06:00 [pubmed]
PHST- 2010/08/06 06:00 [medline]
AID - TAN1390 [pii]
AID - 10.1111/j.1399-0039.2009.01390.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2010 Jan;75(1):30-9. doi: 10.1111/j.1399-0039.2009.01390.x. Epub 
      2009 Oct 30.