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Int J Oncol. 2015 Apr;46(4):1677-84. doi: 10.3892/ijo.2015.2873. Epub 2015 Feb 4.

Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro.

Author information

1
Department of Gynecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China.
2
Cancer Research Institute, Central South University, Changsha, Hunan 410078, P.R. China.

Abstract

Cervical cancer is a potentially preventable disease; however, it is the third most commonly diagnosed cancer and the fourth leading cause of cancer deaths in women worldwide. Cervical cancer is thought to develop through a multistep process involving virus, tumor suppressor genes, proto-oncogenes and immunological factors. It is known that human papillomavirus (HPV) infection is necessary but insufficient to cause malignancy. At present, the etiology of cervical carcinoma remains poorly understood. In this study, we found that the expression of FOS-like antigen-1 (Fra-1) gene was downregulated in cervical cancer compared with the adjacent non-cancerous tissues by RT-qPCR, immunohistochemistry (IHC) and western blotting techniques. To uncover the effect of Fra-1 on cervical cancer, we tested and confirmed that Fra-1 significantly inhibited the proliferation of HeLa cells by MMT assays in vitro. At the same time, overexpression of Fra-1 promoted apoptosis of HeLa cells. To explore the possible mechanism of Fra-1 in cervical cancer, we tested the expression levels of key molecules in p53 signaling pathway by western blotting technology. The results showed that p53 was downregulated in cervical cancer compared with the adjacent non-cancerous tissues, but MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) was upregulated in cervical cancer. In vitro, the p53 was upregulated and MDM2 was downregulated in HeLa cells with Fra-1 overexpression. In summary, our results suggested that Fra-1 expression is low in cervical cancer tissues and promotes apoptosis of cervical cancer cells by p53 signaling pathway.

PMID:
25651840
DOI:
10.3892/ijo.2015.2873
[Indexed for MEDLINE]

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