Abstract

Recent studies have suggested a novel oncogenic role of a bric-a-brac tramtrack broad complex (also known as POZ) domain gene, NAC-1, in ovarian carcinomas. The aim of this study was to clarify the functional role of NAC-1 in human cervical carcinomas. NAC-1 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. NAC-1 gene knockdown using small interfering RNA and a NAC-1 gene transfection system were used to asses NAC-1 function in cervical cancer in vivo. Immunohistochemical and gene expression analysis revealed that NAC-1 is significantly overexpressed in cervical adenocarcinomas and adenosquamous carcinomas compared with squamous cell carcinomas. Patients with squamous cell carcinomas positive for NAC-1 expression who received radiotherapy had significantly shorter overall survival than peers whose tumors did not express NAC-1, and multivariate analysis showed that NAC-1 expression was an independent prognostic factor for overall survival after radiotherapy. Overexpressions of the NAC-1 gene stimulated cell proliferation in cervical carcinoma cells of the TCS, CaSki, and HeLa P3 lines, which do not have endogenous NAC-1 expression. NAC-1 gene knockdown inhibited cell growth and induced apoptosis in HeLa, HeLa TG, and ME180 cells, all of which overexpressed NAC-1. Our findings suggest that NAC-1 may play an important role in cervical carcinomas; moreover, these findings provide a rationale for future development of NAC-1-based therapy for cervical carcinomas that overexpress this candidate oncogene.

Highlights

  • Recent studies have suggested a novel oncogenic role of a bric-a-brac tramtrack broad complex domain gene, NAC-1, in ovarian carcinomas

  • NAC-1 expression is higher in adenocarcinomas/adenosquamous cell carcinomas than in squamous cell carcinomas

  • We reported that NAC-1 is a tumor recurrence – associated gene with oncogenic potential in ovarian cancer [12]

Read more

Summary

Introduction

Recent studies have suggested a novel oncogenic role of a bric-a-brac tramtrack broad complex ( known as POZ) domain gene, NAC-1, in ovarian carcinomas. The bric-a-brac tramtrack broad complex [BTB, known as POZ] gene family is composed of several proteins that share a conserved BTB/POZ protein-protein interaction motif at the NH2 terminal that mediates homodimer or heterodimer formation (2 – 4) These proteins have been shown to participate in a wide variety of cellular functions, including regulation of transcription, cellular proliferation, apoptosis, cell morphology, ion channel assembly, and protein degradation through ubiquitination [2]. Our previous study revealed that NAC-1 is significantly overexpressed in several types of carcinomas [12] To extend these observations to cervical carcinomas, we measured NAC-1 expression levels in cervical carcinoma tissue samples and cell lines and sought to determine the role of NAC1 in cervical cancer

Objectives
Methods
Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.