FOXO1 is a tumor suppressor in cervical cancer

被引:59
作者
Zhang, B. [1 ,2 ]
Gui, L. S. [1 ]
Zhao, X. L. [2 ]
Zhu, L. L. [2 ]
Li, Q. W. [1 ]
机构
[1] Northwest A&F Univ, Coll Anim Sci & Technol, Yangling, Shaanxi, Peoples R China
[2] Jiamusi Univ, Coll Basic Med Sci, Jiamusi, Heilongjiang, Peoples R China
关键词
Cell apoptosis; Cell proliferation; Cervical cancer; Cell cycle; Forkhead box protein 01; Immunohistochemistry; TRANSCRIPTION FACTOR FKHR; HUMAN-PAPILLOMAVIRUS; GENE-EXPRESSION; CELL-CYCLE; APOPTOSIS; CARCINOMA; MECHANISM;
D O I
10.4238/2015.June.18.3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Forkhead box protein O1 (FOXO1) is an important transcriptional regulator of cell proliferation, and is considered essential for tumor growth and progression. However, the function of FOXO1 in human cervical cancer remains unclear. In this study, we investigated the role of FOXO1 in cervical cancer. Our results showed that FOXO1 expression was lower in cervical cancer than in cervical intraepithelial neoplasia and normal cervix by immunohistochemical analysis (P < 0.05). The level of FOXO1 in high-grade lesions was significantly lower than in low-grade lesion (P < 0.05), indicating that deficient expression of FOXO1 is involved in tumor progression and significantly associated with late-stage tumors (P < 0.05), which was further supported by clinicopathological, real-time polymerase chain reaction, and Western blotting analysis. Moreover, we confirmed that the overexpression of FOXO1 remarkably repressed cell growth and blocked cell proliferation, accompanied by cell-cycle arrest in the G(2)/M phase and upregulation of caspases-3 and -9 gene expression. Collectively, our data suggest that FOXO1 plays a vital role in inhibiting cervical cancer development by inducing cell-cycle arrest and apoptosis. FOXO1 expression is a favorable prognostic factor for human cervical cancer.
引用
收藏
页码:6605 / 6616
页数:12
相关论文
共 26 条
[21]   FoxO transcription factors in the maintenance of cellular homeostasis during aging [J].
Salih, Dervis A. M. ;
Brunet, Anne .
CURRENT OPINION IN CELL BIOLOGY, 2008, 20 (02) :126-136
[22]   Human papillomavirus and cervical cancer [J].
Crosbie, Emma J. ;
Einstein, Mark H. ;
Franceschi, Silvia ;
Kitchener, Henry C. .
LANCET, 2013, 382 (9895) :889-899
[23]   The human papillomavirus E6 oncogene dysregulates the cell cycle and contributes to cervical carcinogenesis through two independent activities [J].
Shai, Army ;
Brake, Tiffany ;
Somoza, Chamorro ;
Lambert, Paul F. .
CANCER RESEARCH, 2007, 67 (04) :1626-1635
[24]   Stressing the role of FoxO proteins in lifespan and disease [J].
van der Horst, Armando ;
Burgering, Boudewijn M. T. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (06) :440-450
[25]   A New Fork for Clinical Application: Targeting Forkhead Transcription Factors in Cancer [J].
Yang, Jer-Yen ;
Hung, Mien-Chie .
CLINICAL CANCER RESEARCH, 2009, 15 (03) :752-757
[26]   Improved therapeutic efficacy against murine carcinoma by combining honokiol with gene therapy of PNAS-4, a novel pro-apoptotic gene [J].
Yuan, Zhu ;
Liu, Huanyi ;
Yan, Fei ;
Wang, Yongsheng ;
Gou, Lantu ;
Nie, Chunlai ;
Ding, Zhenyu ;
Lai, Songtao ;
Zhao, Yuwei ;
Zhao, Xinyu ;
Li, Jiong ;
Deng, Hongxin ;
Mao, Yongqiu ;
Chen, Lijuan ;
Wei, Yuquan ;
Zhao, Xia .
CANCER SCIENCE, 2009, 100 (09) :1757-1766