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

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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

Fingerprint

Ubiquitin Thiolesterase
Apoptosis
Breast Neoplasms
MCF-7 Cells
Ubiquitin
Bisbenzimidazole
Cell Line
Neoplasms
1-Phosphatidylinositol 4-Kinase
Ubiquitination
Multiple Drug Resistance
Proteasome Endopeptidase Complex
Cytochromes
Germ Cells
Caspase 3
Small Interfering RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Wang, W. J., Li, Q. Q., Xu, J. D., Cao, X. X., Li, H. X., Tang, F., ... 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
Wang, Wen Juan ; Li, Qing Quan ; Xu, Jing Da ; Cao, Xi Xi ; Li, Hai Xia ; Tang, Feng ; Chen, Qi ; Yang, Jin Ming ; Xu, Zu De ; Liu, Xiu Ping. / Over-expression of Ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells. In: International journal of oncology. 2008 ; Vol. 33, No. 5. pp. 1037-1045.
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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.",
author = "Wang, {Wen Juan} and Li, {Qing Quan} and Xu, {Jing Da} and Cao, {Xi Xi} and Li, {Hai Xia} and Feng Tang and Qi Chen and Yang, {Jin Ming} and Xu, {Zu De} and Liu, {Xiu Ping}",
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Wang, WJ, Li, QQ, Xu, JD, Cao, XX, Li, HX, Tang, F, Chen, Q, Yang, JM, Xu, ZD & Liu, XP 2008, 'Over-expression of Ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells', International journal of oncology, vol. 33, no. 5, pp. 1037-1045. https://doi.org/10.3892/ijo_00000092

Over-expression of Ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells. / Wang, Wen Juan; Li, Qing Quan; Xu, Jing Da; Cao, Xi Xi; Li, Hai Xia; Tang, Feng; Chen, Qi; Yang, Jin Ming; Xu, Zu De; Liu, Xiu Ping.

In: International journal of oncology, Vol. 33, No. 5, 01.12.2008, p. 1037-1045.

Research output: Contribution to journalArticle

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AU - Wang, Wen Juan

AU - Li, Qing Quan

AU - Xu, Jing Da

AU - Cao, Xi Xi

AU - Li, Hai Xia

AU - Tang, Feng

AU - Chen, Qi

AU - Yang, Jin Ming

AU - Xu, Zu De

AU - Liu, Xiu Ping

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