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.
Institute of Physiology, Center for Physiology and Pharmacology, Medical University Vienna, Austria.
C
C
Nemeth
S
S
Humpeler
E
E
Kallay
I
I
Mesteri
M
M
Svoboda
O
O
Rögelsperger
N
N
Klammer
T
T
Thalhammer
C
C
Ekmekcioglu
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D056926:CLOCK Proteins / Q000235:genetics; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D056931:Cryptochromes / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D044122:Receptor, Melatonin, MT1 / Q000032:analysis / Q000235:genetics*
C538963:CRY1 protein, human; D056931:Cryptochromes; D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D056926:CLOCK Proteins; C538943:CLOCK protein, human