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Open Access Research article

Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

Zhengyu Fang1, Wantong Yao2, Yi Xiong1, Jiana Li1, Li Liu1, Lei Shi4, Wei Zhang34, Chao Zhang1, Liping Nie5 and Jun Wan14*

Author Affiliations

1 Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Guangdong Province, Shenzhen, China

2 Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China

3 JNU-HKUST joint lab, Ji-Nan University, Guangdong, China

4 Section of Biochemistry and Cell Biology, Division of Life Science The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong

5 Department of Clinical Laboratory, Shenzhen Hospital, Peking University, Guangdong, China

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BMC Cancer 2011, 11:195  doi:10.1186/1471-2407-11-195

Published: 24 May 2011

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, 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.