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Expression of the bric-a-brac tramtrack broad complex protein NAC-1 in cervical carcinomas seems to correlate with poorer prognosis Yeasmin S; Nakayama K; Ishibashi M; Katagiri A; Iida K; Purwana IN; Nakayama N; Miyazaki KClin Cancer Res 2008[Mar]; 14 (6): 1686-91PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.|Adenocarcinoma/*diagnosis/genetics/mortality/radiotherapy[MESH]|Adult[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Apoptosis/drug effects[MESH]|Carcinoma, Squamous Cell/diagnosis/genetics/mortality/radiotherapy[MESH]|Female[MESH]|Gene Expression Regulation, Neoplastic[MESH]|HeLa Cells[MESH]|Humans[MESH]|Middle Aged[MESH]|Multiprotein Complexes/genetics/metabolism[MESH]|Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism[MESH]|Prognosis[MESH]|RNA, Small Interfering/pharmacology[MESH]|Repressor Proteins/antagonists & inhibitors/genetics/*metabolism[MESH]|Survival Analysis[MESH]|Tumor Cells, Cultured[MESH]|Uterine Cervical Neoplasms/*diagnosis/genetics/mortality/radiotherapy[MESH] |
