attenuated expression of hrh4 in colorectal carcinomas a potential influence on tumor growth and progression减毒的表达hrh4在大肠癌癌潜在影响肿瘤的生长和发展.pdfVIP

Fang et al. BMC Cancer 2011, 11:195 /1471-2407/11/195 RESEARCH ARTICLE Open Access Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression 1 2 1 1 1 4 3,4 1 5 Zhengyu Fang , Wantong Yao , Yi Xiong , Jiana Li , Li Liu , Lei Shi , Wei Zhang , Chao Zhang , Liping Nie and Jun Wan1,4* Abstract Background: Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods: Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results: The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore,