Decreased expression of the melatonin receptor 1 in human colorectal adenocarcinomas.

Melatonin exerts anti-proliferative and pro-apoptotic effects in various cancer cell lines. Furthermore, there is evidence for impaired melatonin secretion in human breast and colorectal cancer. Additionally, several studies revealed a modulated expression of the melatonin receptor 1 (MT1), in human breast cancer specimens. Since melatonin binding sites were already identified in the human intestine, our aim is to identify the expression and to characterize the localization of the MT1 receptor in the human colon and in particular to compare MT1 expression levels between non-malignant and malignant colonic tissue. We assessed MT1 transcript levels with real time RT-PCR in colon adenocarcinomas and the adjacent normal colonic mucosa of 39 patients and observed a significant decrease of MT1 mRNA expression in colorectal cancer compared with the healthy adjacent mucosa tissue (0.67 mean difference, P < 0.0001). The results were confirmed at the protein level by Western blot analysis and by immunohistochemistry. MT1 was localized mainly supranuclear in colonic epithelial cells lining the crypts. We also evaluated mRNA expression of different clock genes in the colon samples and found a significant correlation between MT1 and Cryptochrome 1 (Cry1) expression (P < 0.01 for normal and P < 0.05 for tumour tissue). In conclusion, the decreased expression of MT1 in human colorectal cancer could point to a role of melatonin in this disease.

Coexpression of the melatonin receptor 1 and nestin in human breast cancer specimens.

Activation of the G-protein-coupled receptor (GPCR) for melatonin (MT1) suppresses breast cancer cell growth in experimental models. To elucidate whether MT1 might play a role in cancer cells positive for the stem cell marker nestin, we assessed paired carcinomatous (Ca) and adjacent noncancerous (NCa) samples from 42 patients with primary breast cancer for MT1 and nestin by double immunofluorescence staining and quantitative image analysis with Tissue-Quest software. MT1 was located in luminal and myoepithelial cells in milk ducts and in tumor cells in 40/42 and 39/42 of NCa and Ca specimens, respectively, independent of hormone receptor and HER-2 status. Nestin was located together with MT1 in myoepithelial cells in 38 NCa specimens (total n = 42) and in 18 Ca specimens with intact milk ducts. Quantitative evaluation of selected 16 NCa and Ca samples revealed that MT1 levels were higher in invasive Ca sections than in NCa specimens in eight and lower in six cases. Specimens from higher tumor stages (TII/III) with a higher risk of relapse were associated with MT1/nestin co-staining in more than 10% of tumor cells, whereas a lack of co-staining correlated with lower tumor stages. Abundant expression of MT1 and, particularly, coexpression of MT1 with nestin in invading tumor cells in more advanced tumors suggest an important role for this GPCR in the pathogenesis of breast cancer.