UBE2D3 gene overexpression increases radiosensitivity of EC109 esophageal cancer cells in vitro and in vivo.
Ubiquitin-conjugating enzyme E2D3 (UBE2D3), a key component in ubiquitin (Ub) proteasome system, plays a crucial role in tumorigenesis. We previously found that it is bound to hTERT, and UBE2D3 could attenuate radiosensitivity of human breast cancer cells. Here we investigated a contributing role of UBE2D3 in radiosensitivity of esophageal squamous carcinoma. We demonstrated that the overexpression of UBE2D3 in esophageal squamous carcinoma cells (EC109) resulted in prolonged G1 phase and shortened G2/M phase after irradiation. UBE2D3 overexpression also decreased length of telomere and activity of telomerase. In addition, the overexpression of UBE2D3 increased mRNA expression but decreased protein levels of hTERT in both vitro and vivo systems. Compared with untreated cells, the treatment of UBE2D3 overexpressing cells with the specific proteasome inhibitor (MG132) could up-regulate hTERT. MG132 treatment of UBE2D3 overexpressed cells caused a clear and dramatic increase in the amount of ubiquitinated hTERT species. These findings indicate that UBE2D3 enhances radiosensitivity of EC109 cells by degradating hTERT through the ubiquitin proteolysis pathway.
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.|Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Xiaojia
X
Gao
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Wenbo
W
Wang
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.|Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Hui
H
Yang
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.|Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Lin
L
Wu
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.|Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Zhongshi
Z
He
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.|Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Shuliang
S
Zhou
Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China.|Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Hong
H
Zhao
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Zhenming
Z
Fu
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Fuxiang
F
Zhou
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.|Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Yunfeng
Y
Zhou
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis* / Q000235:genetics*; D054875:Ubiquitination / Q000187:drug effects / Q000528:radiation effects
D012333:RNA, Messenger; C097310:UBE2D3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C509186:TERT protein, human; D019098:Telomerase
UBE2D3; esophageal cancer; hTERT; radiosensitivity; ubiquitin