Biological role and prognostic significance of NAC1 in ovarian cancer.
OBJECTIVE
This study examined the biological and clinical significance of NAC1 expression in ovarian cancer and assessed whether NAC1 has the potential to be a therapeutic target.


METHODS
NAC1 expression and gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected by a retrospective chart review. NAC1 gene knockdown using silencing RNA and a NAC1 gene transfection system were used to assess NAC1 function in ovarian cancer tissue samples.


RESULTS
The frequency of positive NAC1 expression in serous adenocarcinomas (50.0%:22/44) was significantly higher than that in the other histological subtypes (33.3%: 10/30). NAC1 gene amplification was identified in seven (9.5%) of 74 ovarian carcinomas. Positive NAC1 expression significantly correlated with shorter disease-free and overall survival (P = 0.002, P = 0.0048). A multivariate analysis showed that positive NAC1 expression was an independent prognostic factor for disease-free and overall survival after standard platinum-taxane chemotherapy (P = 0.0027, P = 0.0302). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in ovarian cancer cell lines KF28 and TOV-21G, which normally lacked NAC1 expression.


CONCLUSIONS
These findings indicate that NAC1 over-expression is critical to the growth and survival of ovarian cancers. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, NAC1-targeted therapy may benefit ovarian cancer patients with NAC1 expression.
Nakayama
Kentaro
K
Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Shimane, Japan. kn88@med.shimane-u.ac.jp
Rahman
Mohammed Tanjimur
MT
Rahman
Munmun
M
Yeasmin
Shamima
S
Ishikawa
Masako
M
Katagiri
Atsuko
A
Iida
Kouji
K
Nakayama
Naomi
N
Miyazaki
Kohji
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099186:Histone Deacetylase 3
D014408:Biomarkers, Tumor; D006655:Histone Deacetylases; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C516477:NACC1 protein, human; C400300:HDAC4 protein, human