Subcellular localization of MCM2 correlates with the prognosis of ovarian clear cell carcinoma
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Gulinisha Aihemaiti1, Morito Kurata1, Daichi Nogawa1, Akiko Yamamoto1, Tatsunori Mineo1, Iichiroh Onishi1, Yuko Kinowaki1, Xiao-Hai Jin1, Anna Tatsuzawa2,3, Naoyuki Miyasaka3, Masanobu Kitagawa1 and Kouhei Yamamoto1
1Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113–8510, Japan
2Department of Analytical Information of Clinical Laboratory Medicine, Graduate School of Health Care Science, Bunkyo Gakuin University, Tokyo 113–8668, Japan
3Department of Obstetrics and Gynecology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113–8510, Japan
Kouhei Yamamoto, email: firstname.lastname@example.org
Keywords: ovarian cancer; pathology; clinicopathologic study; MCM2; cancer therapy target
Received: February 16, 2018 Accepted: May 27, 2018 Published: June 15, 2018
Highly malignant tumors overexpress the minichromosome maintenance 2 (MCM2) protein in the nucleus, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In this study, we showed that MCM2 is highly expressed in clinical samples of ovarian clear cell carcinoma. Although MCM2 expression was mainly localized to the nuclei as in other cancers, a few cases exhibited cytoplasmic localization of MCM2. Surprisingly, tumor samples with cytoplasmic MCM2 demonstrated excellent prognosis, showing 100% survival during the observation period of more than 200 months. However, cases with nuclear expression of MCM2 exhibited approximately 78% 5-year-survival rate. In a previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70 bound to MCM2, impaired its nuclear translocation, and enhanced DNA damage-induced apoptosis in FLV-infected hematopoietic cells with high levels of MCM2. As expected, clear cell carcinoma cells with cytoplasmic expression of MCM2 exhibited significantly higher apoptotic cell ratio than that of cells with nuclear MCM2 expression. In vitro experiments using ovarian cancer cells with cytoplasmic expression of MCM2 demonstrated that transfection of MCM2-ΔN enhanced DNA damage-induced apoptosis. Therefore, cytoplasmic localization of MCM2 significantly correlated with increased apoptosis in clear cell carcinoma cells, resulting in improved prognosis.
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