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学科主题临床医学
Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression
Fang, Zhengyu1; Yao, Wantong2; Xiong, Yi1; Li, Jiana1; Liu, Li1; Shi, Lei4; Zhang, Wei3,4; Zhang, Chao1; Nie, Liping5; Wan, Jun1,4
刊名BMC CANCER
2011-05-24
DOI10.1186/1471-2407-11-195
11
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]CELL-CYCLE ARREST ; RECEPTOR ANTAGONISTS ; AUTOCRINE REGULATOR ; H4 RECEPTORS ; CANCER CELLS ; HISTAMINE ; 5-FLUOROURACIL ; PROLIFERATION ; INHIBITORS ; INDUCTION
英文摘要

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, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells.

Conclusion: The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

语种英语
WOS记录号WOS:000292243600001
项目编号81001173/H1622 ; JC201005260215A
资助机构National Natural Science Foundation of China ; Fundamental Research Plan of Shenzhen City
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59061
专题北京大学深圳医院
作者单位1.Shenzhen PKU HKUST Med Ctr, Biomed Res Inst, Shenzhen, Guangdong, Peoples R China
2.Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China
3.Ji Nan Univ, JNU HKUST Joint Lab, Guangzhou, Guangdong, Peoples R China
4.Hong Kong Univ Sci & Technol, Div Life Sci, Sect Biochem & Cell Biol, Kowloon, Hong Kong, Peoples R China
5.Peking Univ, Shenzhen Hosp, Dept Clin Lab, Guangzhou, Guangdong, Peoples R China
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GB/T 7714
Fang, Zhengyu,Yao, Wantong,Xiong, Yi,et al. Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression[J]. BMC CANCER,2011,11.
APA Fang, Zhengyu.,Yao, Wantong.,Xiong, Yi.,Li, Jiana.,Liu, Li.,...&Wan, Jun.(2011).Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression.BMC CANCER,11.
MLA Fang, Zhengyu,et al."Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression".BMC CANCER 11(2011).
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