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Synaptonemal complex protein 3 is a prognostic marker in cervical cancer.

Authors
 Hanbyoul Cho  ;  Kyung Hee Noh  ;  Joon-Yong Chung  ;  Mikiko Takikita  ;  Eun Joo Chung  ;  Bo Wook Kim  ;  Stephen M. Hewitt  ;  Tae Woo Kim  ;  Jae-Hoon Kim 
Citation
 PLOS ONE, Vol.9(6) : e98712, 2014 
Journal Title
 PLOS ONE 
Issue Date
2014
MeSH
Adult ; Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism* ; Carcinogenesis ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Middle Aged ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism* ; Phenotype ; Phosphoproteins/metabolism ; Prognosis ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Uterine Cervical Neoplasms/diagnosis* ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/metabolism* ; Uterine Cervical Neoplasms/pathology ; Young Adult
Abstract
Synaptonemal complex protein 3 (SCP3), a member of Cor1 family, is up-regulated in various cancer cells; however, its oncogenic potential and clinical significance has not yet been characterized. In the present study, we investigated the oncogenic role of SCP3 and its relationship with phosphorylated AKT (pAKT) in cervical neoplasias. The functional role of SCP3 expression was investigated by overexpression or knockdown of SCP3 in murine cell line NIH3T3 and human cervical cancer cell lines CUMC6, SiHa, CaSki, and HeLa both in vitro and in vivo. Furthermore, we examined SCP3 expression in tumor specimens from 181 cervical cancer and 400 cervical intraepithelial neoplasia (CIN) patients by immunohistochemistry and analyzed the correlation between SCP3 expression and clinicopathologic factors or survival. Overexpression of SCP3 promoted AKT-mediated tumorigenesis both in vitro and in vivo. Functional studies using NIH3T3 cells demonstrated that the C-terminal region of human SCP3 is important for AKT activation and its oncogenic potential. High expression of SCP3 was significantly associated with tumor stage (P = 0.002) and tumor grade (P<0.001), while SCP3 expression was positively associated with pAKT protein level in cervical neoplasias. Survival times for patients with cervical cancer overexpressing both SCP3 and pAKT (median, 134.0 months, n = 68) were significantly shorter than for patients with low expression of either SCP3 or pAKT (161.5 months, n = 108) as determined by multivariate analysis (P = 0.020). Our findings suggest that SCP3 plays an important role in the progression of cervical cancer through the AKT signaling pathway, supporting the possibility that SCP3 may be a promising novel cancer target for cervical cancer therapy.
Files in This Item:
T201401601.pdf Download
DOI
10.1371/journal.pone.0098712
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
Cho, Hanbyoul(조한별) ORCID logo https://orcid.org/0000-0002-6177-1648
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98859
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