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]
Summary
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
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