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学科主题: 临床医学
题名:
Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression
作者: 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
发表日期: 2011-05-24
DOI: 10.1186/1471-2407-11-195
卷: 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
所属项目编号: 81001173/H1622 ; JC201005260215A
项目资助者: National Natural Science Foundation of China ; Fundamental Research Plan of Shenzhen City
WOS记录号: WOS:000292243600001
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59061
Appears in Collections:北京大学深圳医院_期刊论文

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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

Recommended Citation:
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.
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