Expression of melatonin receptor <scp>MT</scp>1 in cells of human invasive ductal breast carcinoma

Karolina Jabłońska(Wroclaw Medical University), Bartosz Puła(Wroclaw Medical University), Agata Zemła(Wroclaw Medical University), Tomasz B. Owczarek(Wrocław University of Environmental and Life Sciences), Andrzej Wojnar, Janusz Ryś(The Maria Sklodowska-Curie National Research Institute of Oncology), Aleksandra Ambicka(The Maria Sklodowska-Curie National Research Institute of Oncology), Marzenna Podhorska‐Okołów(Wroclaw Medical University), Maciej Ugorski(Wrocław University of Environmental and Life Sciences), Piotr Dzięgiel(Wroclaw Medical University)
Journal of Pineal Research
December 13, 2012
Cited by 68

Abstract

In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC.


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