Over-expression of Ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells

Wen Juan Wang, Qing Quan Li, Jing Da Xu, Xi Xi Cao, Hai Xia Li, Feng Tang, Qi Chen, Jin Ming Yang, Zu De Xu, Xiu Ping Liu

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Ubiquitin carboxy terminal hydrolase-L1 (UCH-L1) belongs to the UCH proteases family that deubiquitinates ubiquitin-protein conjugates in the ubiquitin-proteasome system. Previous research showed that UCH-L1 was expressed in mouse retinal cells and testicular germ cells, and its function was associated with apoptosis. But it is still unclear whether UCH-L1 is concerned with apoptosis in tumor cells. In order to clarify the role of UCH-L1 in tumor cells, multi-drug resistance (MDR) human breast carcinoma cell line MCF7/Adr, that expresses relatively high UCH-L1, and its parental cell line MCF7, that expresses relatively low UCH-L1, were chosen for this study. We transfected pcDNA3.1-UCH-L1 plasmid and UCH-L1 siRNA into MCF7 and MCF7/Adr cells, respectively. Using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, Western blot, Hoechst 33258 staining assay and flow cytometry, we found that over-expression of UCH-L1 in MCF7 cells induced apoptosis. On the other hand, silencing of UCH-L1 in MCF7/Adr cells led to the opposite effect. Moreover, to explore the mechanism underling these observations, we further investigated the expression of phospho-Akt and its downstream signal phospho-IκB-α and other signal molecules including Fas, Fas-L, Trail, DR4, DR5, Bax, cytochrome C, active caspase-3, phospho-p53, phospho-Mdm-2, Bcl-2, Bcl-xL, p21 and p27. The results indicated that the process of apoptosis triggered by UCH-L1 is, at least in part, probably through Phosphoinositide 3-kinase (PI3K)/Akt signal pathway. Our findings suggest that modulating the ubiquitination and deubiquitination pathway could be a novel method for tumor therapy.

Original languageEnglish (US)
Pages (from-to)1037-1045
Number of pages9
JournalInternational journal of oncology
Volume33
Issue number5
DOIs
StatePublished - Dec 1 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Over-expression of Ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Wang, W. J., Li, Q. Q., Xu, J. D., Cao, X. X., Li, H. X., Tang, F., Chen, Q., Yang, J. M., Xu, Z. D., & Liu, X. P. (2008). Over-expression of Ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells. International journal of oncology, 33(5), 1037-1045. https://doi.org/10.3892/ijo_00000092