Open AccessSuppression of REV 7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells
Author(s) -
Niimi Kaoru,
Murakumo Yoshiki,
Watanabe Naoki,
Kato Takuya,
Mii Shinji,
Enomoto Atsushi,
Asai Masato,
Asai Naoya,
Yamamoto Eiko,
Kajiyama Hiroaki,
Shibata Kiyosumi,
Kikkawa Fumitaka,
Takahashi Masahide
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12390
Subject(s) - gene knockdown , cisplatin , carcinogenesis , cell growth , cancer research , ovarian cancer , cell cycle , apoptosis , cell , immunohistochemistry , biology , chemistry , cancer , medicine , immunology , chemotherapy , biochemistry , genetics
Human REV 7 (also known as MAD 2L2 and MAD 2B) is involved in DNA repair, cell cycle regulation, gene transcription, and carcinogenesis. In this study, we evaluated the expression of REV 7 in epithelial ovarian cancer ( EOC ) and analyzed the association between its expression and chemosensitivity in ovarian clear cell carcinoma ( CCC ) cells. Expression of REV 7 in human EOC tissues was assessed by immunohistochemical staining. Expression was detected in the majority of EOC s (92.0%) with especially high levels of expression frequently observed in CCC s (73.5%) compared with that of non‐ CCC s (53.4%). Enhanced immunoreactivity to REV 7 was associated with poor prognosis represented by reduced progression‐free survival in advanced stage (stage II – IV ) EOC as assessed using Kaplan–Meier curves and log–rank tests. The effects of REV 7 knockdown on cell proliferation and chemosensitivity in CCC cells were also analyzed in vitro and in vivo . Knockdown of REV 7 in CCC cells decreased cell proliferation without affecting cell cycle distribution. Additionally, the number of apoptotic cells and DNA damaged cells were increased after cisplatin treatment. In a nude mouse tumor xenograft model, inoculated REV 7‐knockdown tumors showed significantly reduced tumor volumes after cisplatin treatment compared with those of the control group. These findings indicate that depletion of REV 7 enhances sensitivity to cisplatin treatment in CCC , suggesting that REV 7 is a candidate molecular target in CCC management.