Gankyrin is frequently overexpressed in cervical high grade disease and is associated with cervical carcinogenesis and metastasis.

Yuan Liu,Sufang Wu,Jiawen Zhang,Zhiqiang Liu,Ding Ma,Zhenbo Zhang,Yongbin Yang,Youji Feng,Wenyan Qian,Yu Dong,Javier S Castresana

doi:10.1371/journal.pone.0095043

Abstract

Our previous studies have showed that Gankyrin expression is correlated with a malignant phenotype in endometrial carcinoma. Here, we investigated the possible role of Gankyrin in cervical disease. The increasing protein level of Gankyrin was observed in high-grade cervical intraepithelial neoplasia and carcinoma compared with benign cervical tissues and low-grade cervical intraepithelial neoplasia. In para-carcinoma tissues, it was found interestingly that there was no lymph node metastasis when nuclei Gankyrin was positively expressed, but lymph node metastasis rate was 30% (6/20) when nuclei Gankyrin was negatively expressed. In vitro, the transfection of Gankyrin resulted in markedly up-regulating of Vimentin, β-catenin and Twist2, as well as down-regulating of E-cadherin in cervical carcinoma cells. Our results suggested that Gankyrin may be functional in cervical carcinogenesis and metastasis.

Highlights

Cervical carcinoma is the third leading cause of cancer-related death in women worldwide
Compared with normal cervix tissues, cervical intraepithelial neoplasia (CIN) II–III and cervical carcinoma tissues had stronger positive IHC staining of Gankyrin, which means the higher expression of Gankyrin protein in cervical precancerous lesion and carcinoma tissues (Table S1)
In further investigation of the role of Gankyrin in cervical carcinoma, we found that the positive expression rate of Gankyrin had no significant difference between the patients of less than 45 years old and over 45 years old, and neither no significant relationship with histopathological grade and the metastasis of lymph node (p.0.05) (Table 1)

Summary

Introduction

Cervical carcinoma is the third leading cause of cancer-related death in women worldwide. The American Cancer Society estimates that 12,340 women will be diagnosed with invasive cervical cancer, and 4,030 women will die from the disease in 2013 [1]. There are more than 130 thousand cases of cervical cancer newly found in China every year, which accounts for 1/4 of all the cases of cervical cancer around the world, and more than 30 thousand of them are being died. More than 99% of cervical carcinomas are positive for high-risk human papillomaviruses (HPVs) [2]. Despite extensive studies focused on the mechanisms of HPV-induced cervical carcinogenesis, the downstream signaling events mediated by other important factors remain obscure

Methods

Results

Conclusion