title: Deletion and down-regulation of HRH4 gene in gastric carcinomas: a potential correlation with tumor progression.
abstract: BACKGROUND
  Histamine is an established growth factor for gastrointestinal malignancies. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Histamine receptor H4 (HRH4), the newest member of the histamine receptor family, is positively expressed on the epithelium of the gastrointestinal tract, and its function remains to be elucidated. Previously, we reported the decreased expression of HRH4 in colorectal cancers and revealed its correlation with tumor proliferation. In the current study, we aimed to investigate the abnormalities of HRH4 gene in gastric carcinomas (GCs).
  
  
  RESULTS
  We analyzed H4R expression in collected GC samples by quantitative PCR, Western blot analysis, and immunostaining. Our results showed that the protein and mRNA levels of HRH4 were reduced in some GC samples, especially in advanced GC samples. Copy number decrease of HRH4 gene was observed (17.6%, 23 out of 131), which was closely correlated with the attenuated expression of H4R. In vitro studies, using gastric cancer cell lines, showed that the alteration of HRH4 expression on gastric cancer cells influences tumor growth upon exposure to histamine.
  
  
  CONCLUSIONS
  We show for the first time that deletion of HRH4 gene is present in GC cases and is closely correlated with attenuated gene expression. Down-regulation of HRH4 in gastric carcinomas plays a role in histamine-mediated growth control of GC cells.
authors.affiliation: Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiong
authors.forename: Jiana
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Luo
authors.initials: L
authors.lastname: Wang
authors.forename: Manhui
authors.initials: M
authors.lastname: Li
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Fang
mesh_terms: D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056915:DNA Copy Number Variations / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000235:genetics; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011968:Receptors, Histamine / Q000235:genetics*; D000074040:Receptors, Histamine H4; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; C418607:HRH4 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine