RRC ID 58071
著者 Nakade H, Migita K, Matsumoto S, Wakatsuki K, Kunishige T, Miyao S, Sho M.
タイトル Overexpression of Cullin4A correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma.
ジャーナル Int J Clin Oncol
Abstract BACKGROUND:Cullin4A (CUL4A), which is a component of E3 ubiquitin ligase, is implicated in many cellular events. Although the altered expression of CUL4A has been reported in several human cancers, the role of CUL4A in esophageal cancer remains unknown.
METHODS:We investigated the CUL4A expression in primary esophageal squamous cell carcinoma (ESCC) tissue specimens from 120 patients by immunohistochemistry and explored its clinical relevance and prognostic value. Furthermore, the effect of the expression of CUL4A on cancer cell proliferation was analyzed in vitro using an siRNA silencing technique.
RESULTS:The higher expression of CUL4A was significantly associated with a deeper depth of tumor invasion (P < 0.001) and the presence of venous invasion (P = 0.014). The disease-specific survival (DSS) rate in patients with tumors that showed high CUL4A expression levels was significantly lower than that in patients whose tumors showed low CUL4A expression levels (P = 0.001). Importantly, the CUL4A status was identified as an independent prognostic factor for DSS (P = 0.045). Our results suggested that the CUL4A expression has significant prognostic value in ESCC. Furthermore, CUL4A gene silencing significantly inhibited the proliferation of ESCC cells in vitro. In addition, the knockdown of the CUL4A expression induced G1 phase arrest and increased the p21 and p27 protein levels.
CONCLUSIONS:CUL4A might play an important role in regulating the proliferation of ESCC cells and promoting the development of postoperative recurrence.
巻・号 25(3)
ページ 446-455
公開日 2020-3-1
DOI 10.1007/s10147-019-01547-2
PII 10.1007/s10147-019-01547-2
PMID 31535245
MeSH Aged Biomarkers, Tumor / genetics Cell Proliferation / genetics Cullin Proteins / genetics* Cullin Proteins / metabolism Esophageal Neoplasms / genetics* Esophageal Neoplasms / mortality* Esophageal Neoplasms / pathology Esophageal Neoplasms / surgery Esophageal Squamous Cell Carcinoma / genetics* Esophageal Squamous Cell Carcinoma / mortality* Esophageal Squamous Cell Carcinoma / pathology Esophageal Squamous Cell Carcinoma / surgery Female Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Male Middle Aged Neoplasm Recurrence, Local Prognosis RNA, Small Interfering
IF 2.879
引用数 1
リソース情報
ヒト・動物細胞 MKN74(RCB1002)