Purpose: The human mineralocorticoid (MR) receptor is a nuclear receptor mediating aldosterone action and is widely represented in colorectal mucosa. Previous reports revealed a direct effect of steroid hormones on colon cell proliferation, mediated by specific growth factors, although inconsistent data still exist regarding MR. In order to evaluate a potential contribution of MR to cancer progression we examined the expression of MR receptor mRNA in both colorectal cancer and normal mucosa.
Methods: Human colorectal cancer tissue and adjacent normal mucosa were harvested from 27 consecutive patients (male/female: 13/14; mean age 67, range 45-86 years) with colon (n=16) and rectal neoplasia (n=11). MR receptor mRNA expression was determined by real-time reverse transcriptase polymerase chain reaction and correlated with clinico-pathological parameters.
Results: We analysed one Stage 0 (Tis), five Stage 1, ten Stage 2, eight Stage 3, and three Stage 4 (AJCC/TNM system) colorectal tumors. A decline of MR receptor mRNA expression was observed in all tumors compared to normal mucosa samples. The mean value of the cancer:mucosa MR expression ratio was 0.178±0.29, meaning that the MR receptor was on average 6 fold less expressed in cancer compared to the normal mucosa, irrespective of the tumor's location, size, differentiation and stage. In particular, the cancer:mucosa MR receptor expression ratio was 0.132 in Stage 0 (Tis) and a mean of 0.074 in Stage 1 cases.
Conclusions: This is the first report examining MR receptor mRNA expression in human colorectal cancer compared to normal mucosa. These findings are compatible with the hypothesis that reduction of MR receptor expression may be one of the early events involved in colorectal cancer progression. Further studies examining the relationship of the MR receptor with growth factors such as vascular endothelial growth factor and epithelial growth factor are required in order to explore a potential tumor-suppressive function in human colorectal cancer.