Expression of the bric-a-brac tramtrack broad complex protein NAC-1 in cervical carcinomas seems to correlate with poorer prognosis.
OBJECTIVE
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.


METHODS
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.
Yeasmin
Shamima
S
Department of Obstetrics and Gynecology, Shimane University School of Medicine, Shimane, Japan.
Nakayama
Kentaro
K
Ishibashi
Masako
M
Katagiri
Atsuko
A
Iida
Kouji
K
Purwana
Indri Nuryani
IN
Nakayama
Naomi
N
Miyazaki
Kohji
K
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy
D046912:Multiprotein Complexes; C516477:NACC1 protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins