Melatonin receptors, melatonin metabolizing enzymes and cyclin D1 in human breast cancer

• Published in: Journal of receptors and signal transduction Vol. 31; no. 2; p. 180
• Main Authors: Rögelsperger, Olga, Wlcek, Katrin, Ekmekcioglu, Cem, Humpeler, Susanne, Svoboda, Martin, Königsberg, Robert, Klimpfinger, Martin, Jäger, Walter, Thalhammer, Theresia
• Format: Journal Article
• Language: English
• Published: England 01.04.2011
• Subjects: Biotransformation; Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cyclin D1 - genetics; Cyclin D1 - metabolism; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Melatonin - metabolism; Neoplasm Invasiveness; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Receptor, Melatonin, MT1 - genetics; Receptor, Melatonin, MT1 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 1532-4281
• DOI: 10.3109/10799893.2011.557734

Melatonin suppresses breast cancer cell proliferation by inhibiting the upregulation of estrogen-induced cyclin D1 via its G-protein-coupled receptor MT1. Additionally, melatonin stimulates the expression of the estrogen sulfotransferase, SULT1E1. However, metabolism of melatonin via 6-hydroxylation by CYP1A1/1A2 and subsequent sulfonation by SULT1A1/1A3 decreases its intracellular concentration. This could have a negative impact on its oncostatic action in breast cancer. In this pilot study, we performed immunohistochemical (IHC) analysis of MT1 and cyclin D1 in breast cancer specimens from 33 patients. Also, we investigated the expression of CYP1A1/1A2, SULT1A1/1A3/1E1,and cyclin D1 in cancer (CANC) and adjacent non-cancer (NCANC) specimens from 10 representative breast cancer patients using quantitative real-time reverse transcription polymerase chain reaction. CYP1A1-mRNA-expression was found only in three CANC and in one NCANC. CYP1A2 mRNA was below the detection limit in all patients. SULT1A1 was observed only in two of the 10 CANC and one of the 10 NCANC specimens. But, all 10 CANC and NCANC samples showed high SULT1A3 levels. Cyclin D1 mRNA levels were found in all 10 CANC and NCANC specimens. Furthermore, IHC-staining of cyclin D1 was observed in 27 of 33 CANC and correlated positively with estrogen receptor positivity (p = 0.015). The low or even absent expression of CYP1A1 or CYP1A2 in breast cancer specimens suggested that melatonin might be involved in cell cycle arrest.