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Abstract
BackgroundHistamine 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).Methodology/Principal FindingsWe 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/SignificanceWe 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.
Highlights
Histamine is a ubiquitous chemical messenger that has been demonstrated to be involved in cell proliferation, embryonic development, and tumor growth
It was found that mRNA levels of Histamine receptor H4 (HRH4) were reduced in the gastric carcinomas (GCs) samples compared to adjacent normal tissues (ANTs) (Figure 1B)
The relevance of HRH4 abnormalities in colorectal cancer has been reported by different groups [16,17]
Summary
Histamine is a ubiquitous chemical messenger that has been demonstrated to be involved in cell proliferation, embryonic development, and tumor growth These various biological effects are mediated through the activation of specific histamine receptors (H1, H2, H3 and H4) that differ in their tissue expression patterns and functions [1]. Through these pharmacologically distinct receptors, histamine may act as an autocrine or paracrine growth factor that increases proliferation rate in malignant tissues [2,3,4]. We aimed to investigate the abnormalities of HRH4 gene in gastric carcinomas (GCs)
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