Up-regulation of Transcription Factor 3 Is Correlated With Poor Prognosis in Cervical Carcinoma.

Abstract

Transcription factor 3 (TCF3, or E2A) is a multifunctional bHLH (basic helix loop helix) transcription factor. The role of TCF3 expression in cancer and the multiple cell signaling pathways that regulate or are influenced by TCF3 are unclear. Therefore, the expression level of TCF3 in patients with cervical squamous cell carcinoma (CSCC) is discussed in this study. Total RNA was extracted using real-time quantitative reverse transcription-polymerase chain reaction. Western blotting was applied to confirm the results. Immunohistochemistry was used to characterize the expression patterns of TCF3 in CSCC specimens. The close relationship between the expression levels of TCF3 and the 5-year overall survival time was described by survival curves. The association between TCF3 expression and clinicopathological characteristics of 119 CSCC patients was analyzed by Chi-square, Fisher exact test, and Cox regression analysis. TCF3 was overexpressed or inhibited by plasmid transfection, and the proliferation, invasion, and migration of cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, and Transwell assays. The expression of TCF3 was higher in CSCC tissues than in nonmalignant cervical tissues. Messenger RNA (mRNA) and protein in patient tissues were increased compared with nonmalignant cervical tissues. Moreover, the level of expression in early-stage disease was higher than in the advanced stage. From FIGO (International Federation of Gynecology and Obstetrics) stages I to IV, immunohistochemistry staining intensity gradually increased. A high level of expression was closely related to clinical stages. The expression of TCF3 was negatively correlated with overall survival time. TCF3 can promote HeLa cell growth, invasion, and migration in vitro. Based on our results, TCF3 is clearly associated with the progression of CSCC. This is the first time that it has been reported that TCF3 can act as a tumor promoter in cervical cancer and thus might be of great significance in the prognosis of CSCC.