Adiponectin receptors are downregulated in human gastric cancer.

BACKGROUND

Adiponectin has been shown to have suppressive effects on tumor development, but the expression of adiponectin receptors in tumor tissue has not been fully elucidated. The purpose of this study was to quantitatively evaluate the expression of two adiponectin receptors, AdipoR1 and AdipoR2, in gastric cancer tissue.

METHODS

The mRNA levels of AdipoR1 and AdipoR2 were evaluated by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining in 67 gastric cancer tissues and their normal counterparts. In addition, the effects of cytokines on AdipoR1 and AdipoR2 expression in cultured gastric cancer cells were examined.

RESULTS

As compared to findings in the normal counterparts, AdipoR1 mRNA expression, standardized by β-actin mRNA, tended to be lower (cancer 0.488 ± 0.039, normal 0.955 ± 0.281, p = 0.0726) and AdipoR2 expression was significantly lower (0.818 ± 0.081, 1.500 ± 0.222, p = 0.0035) in gastric cancer tissue. Immunohistochemical examination showed the same tendency for AdipoR1 and AdipoR2 expression in epithelial cells. Moreover, AdipoR2 was strongly expressed in interstitial cells. However, the expression levels of these receptors did not show a strong correlation with various pathological factors. An in vitro experiment using two gastric cancer cell lines, MKN-74 and NUGC-3, showed that the expression levels of AdipoR1 and AdipoR2 were significantly decreased by transforming growth factor (TGF)-β in a dose-dependent manner.

CONCLUSIONS

Two major adiponectin receptors were decreased in gastric cancer as compared to findings in normal gastric epithelium. TGF-β may be involved in this receptor downregulation. This downregulation may be an ideal strategy for cancer cells to escape the antiproliferative effects of adiponectin in the initial phase of tumor development.