Subcellular localization of MCM2 correlates with the prognosis of ovarian clear cell carcinoma

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

Oncotarget - 9(2018), 46 vom: 15. Juni, Seite 28213-28225

Sprache:

Englisch

Beteiligte Personen:

Aihemaiti, Gulinisha [VerfasserIn]
Kurata, Morito [VerfasserIn]
Nogawa, Daichi [VerfasserIn]
Yamamoto, Akiko [VerfasserIn]
Mineo, Tatsunori [VerfasserIn]
Onishi, Iichiroh [VerfasserIn]
Kinowaki, Yuko [VerfasserIn]
Jin, Xiao-Hai [VerfasserIn]
Tatsuzawa, Anna [VerfasserIn]
Miyasaka, Naoyuki [VerfasserIn]
Kitagawa, Masanobu [VerfasserIn]
Yamamoto, Kouhei [VerfasserIn]

Links:

Volltext

Themen:

Cancer therapy target
Clinicopathologic study
Journal Article
MCM2
Ovarian cancer
Pathology

Anmerkungen:

Date Revised 20.11.2019

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.18632/oncotarget.25613

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM286063689