title: Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas.
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.
authors: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Shimane 6938501, Japan.
authors: Shamima
authors: S
authors: Yeasmin
authors: Kentaro
authors: K
authors: Nakayama
authors: Mohammed Tanjimur
authors: MT
authors: Rahman
authors: Munmun
authors: M
authors: Rahman
authors: Masako
authors: M
authors: Ishikawa
authors: Atsuko
authors: A
authors: Katagiri
authors: Kouji
authors: K
authors: Iida
authors: Naomi
authors: N
authors: Nakayama
authors: Yoshiro
authors: Y
authors: Otuski
authors: Hiroshi
authors: H
authors: Kobayashi
authors: Satoru
authors: S
authors: Nakayama
authors: Kohji
authors: K
authors: Miyazaki
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000818:Animals; D017209:Apoptosis; D018196:Carcinoma, Adenosquamous / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D055503:Protein Multimerization; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C516477:NACC1 protein, human; C400300:HDAC4 protein, human