RRC ID 38552
Author Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Otuski Y, Kobayashi H, Nakayama S, Miyazaki K.
Title Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas.
Journal Hum Pathol
Abstract This study examined the biological and clinical significance of NAC1 (nucleus accumbens associated 1) expression in both cervical squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. Using immunohistochemistry, the frequency of positive NAC1 expression in adenocarcinomas/adenosquamous carcinomas (31.0%; 18/58) was significantly higher than that in squamous cell carcinomas (16.2%; 12/74) (P = .043). NAC1 gene amplification was identified by fluorescence in situ hybridization in 5 (7.2%) of 69 squamous cell carcinomas. NAC1 amplification was not identified in the adenocarcinomas (0%; 0/58). Positive NAC1 expression was significantly correlated with shorter overall survival in squamous cell carcinomas (P < .0001). A multivariate analysis showed that positive NAC1 expression in squamous cell carcinomas was an independent prognostic factor for overall survival after standard radiotherapy (P = .0003). In contrast to squamous cell carcinomas, positive NAC1 expression did not correlate with shorter overall survival in adenocarcinomas/adenosquamous carcinomas (P = .317). 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 the cervical cancer cell lines TCS and Hela P3, which normally lack NAC1 expression. These findings indicate that NAC1 overexpression is critical to the growth and survival of cervical carcinomas irrespective of histologic type. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, cervical carcinoma patients with NAC1 expression may benefit from a targeted therapy irrespective of histologic type.
Volume 43(4)
Pages 506-19
Published 2012-4-1
DOI 10.1016/j.humpath.2011.05.021
PII S0046-8177(11)00247-4
PMID 21889186
MeSH Adenocarcinoma / metabolism* Adenocarcinoma / pathology Adenocarcinoma / therapy Animals Apoptosis Carcinoma, Adenosquamous / metabolism* Carcinoma, Adenosquamous / pathology Carcinoma, Adenosquamous / therapy Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Carcinoma, Squamous Cell / therapy Cell Movement Cell Proliferation Female Follow-Up Studies HeLa Cells Histone Deacetylases / chemistry Humans Mice Mice, Inbred BALB C Mice, Nude Middle Aged Neoplasm Invasiveness Neoplasm Proteins / chemistry Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Prognosis Protein Multimerization RNA Interference RNA, Neoplasm / genetics Repressor Proteins / chemistry Repressor Proteins / genetics Repressor Proteins / metabolism* Uterine Cervical Neoplasms / metabolism* Uterine Cervical Neoplasms / pathology Uterine Cervical Neoplasms / therapy
IF 2.735
Times Cited 26
WOS Category PATHOLOGY
Resource
Human and Animal Cells