The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma

Chien Feng Li, Wen Jeng Wu, Wen Ren Wu, Yu Jing Liao, Lih Ren Chen, Chun Nung Huang, Ching Chia Li, Wei Ming Li, Hsuan Ying Huang, Yi Ling Chen, Shih Shin Liang, Nan Haw Chow, Yow Ling Shiue

研究成果: Article

26 引文 (Scopus)

摘要

In this study, we report that EMP2 plays a tumor suppressor role by inducing G2/M cell cycle arrest, suppressing cell viability, proliferation, colony formation/ anchorage-independent cell growth via regulation of G2/M checkpoints in distinct urinary bladder urothelial carcinoma (UBUC)-derived cell lines. Genistein treatment or exogenous expression of the cAMP responsive element binding protein 1 (CREB1) gene in different UBUC-derived cell lines induced EMP2 transcription and subsequent translation. Mutagenesis on either or both cAMP-responsive element(s) dramatically decreased the EMP2 promoter activity with, without genistein treatment or exogenous CREB1 expression, respectively. Significantly correlation between the EMP2 immunointensity and primary tumor, nodal status, histological grade, vascular invasion and mitotic activity was identified. Multivariate analysis further demonstrated that low EMP2 immunoexpression is an independent prognostic factor for poor disease-specific survival. Genistein treatments, knockdown of EMP2 gene and double knockdown of CREB1 and EMP2 genes significantly inhibited tumor growth and notably downregulated CREB1 and EMP2 protein levels in the mice xenograft models. Therefore, genistein induced CREB1 transcription, translation and upregulated pCREB1(S133) protein level. Afterward, pCREB1(S133) transactivated the tumor suppressor gene, EMP2, in vitro and in vivo. Our study identified a novel transcriptional target, which plays a tumor suppressor role, of CREB1.

原文English
頁(從 - 到)9220-9239
頁數20
期刊Oncotarget
6
發行號11
DOIs
出版狀態Published - 2015 一月 1

指紋

Carrier Proteins
Urinary Bladder
Genistein
Carcinoma
Neoplasms
G2 Phase Cell Cycle Checkpoints
Gene Knockdown Techniques
Cell Line
Growth
Tumor Suppressor Genes
Heterografts
Mutagenesis
Genes
Blood Vessels
epithelial membrane protein-1
Cell Survival
Proteins
Down-Regulation
Multivariate Analysis
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Oncology

引用此文

Li, Chien Feng ; Wu, Wen Jeng ; Wu, Wen Ren ; Liao, Yu Jing ; Chen, Lih Ren ; Huang, Chun Nung ; Li, Ching Chia ; Li, Wei Ming ; Huang, Hsuan Ying ; Chen, Yi Ling ; Liang, Shih Shin ; Chow, Nan Haw ; Shiue, Yow Ling. / The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma. 於: Oncotarget. 2015 ; 卷 6, 編號 11. 頁 9220-9239.
@article{fd9fd10a57cf4ce48c2c5fde8c4730ef,
title = "The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma",
abstract = "In this study, we report that EMP2 plays a tumor suppressor role by inducing G2/M cell cycle arrest, suppressing cell viability, proliferation, colony formation/ anchorage-independent cell growth via regulation of G2/M checkpoints in distinct urinary bladder urothelial carcinoma (UBUC)-derived cell lines. Genistein treatment or exogenous expression of the cAMP responsive element binding protein 1 (CREB1) gene in different UBUC-derived cell lines induced EMP2 transcription and subsequent translation. Mutagenesis on either or both cAMP-responsive element(s) dramatically decreased the EMP2 promoter activity with, without genistein treatment or exogenous CREB1 expression, respectively. Significantly correlation between the EMP2 immunointensity and primary tumor, nodal status, histological grade, vascular invasion and mitotic activity was identified. Multivariate analysis further demonstrated that low EMP2 immunoexpression is an independent prognostic factor for poor disease-specific survival. Genistein treatments, knockdown of EMP2 gene and double knockdown of CREB1 and EMP2 genes significantly inhibited tumor growth and notably downregulated CREB1 and EMP2 protein levels in the mice xenograft models. Therefore, genistein induced CREB1 transcription, translation and upregulated pCREB1(S133) protein level. Afterward, pCREB1(S133) transactivated the tumor suppressor gene, EMP2, in vitro and in vivo. Our study identified a novel transcriptional target, which plays a tumor suppressor role, of CREB1.",
author = "Li, {Chien Feng} and Wu, {Wen Jeng} and Wu, {Wen Ren} and Liao, {Yu Jing} and Chen, {Lih Ren} and Huang, {Chun Nung} and Li, {Ching Chia} and Li, {Wei Ming} and Huang, {Hsuan Ying} and Chen, {Yi Ling} and Liang, {Shih Shin} and Chow, {Nan Haw} and Shiue, {Yow Ling}",
year = "2015",
month = "1",
day = "1",
doi = "10.18632/oncotarget.3312",
language = "English",
volume = "6",
pages = "9220--9239",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "11",

}

Li, CF, Wu, WJ, Wu, WR, Liao, YJ, Chen, LR, Huang, CN, Li, CC, Li, WM, Huang, HY, Chen, YL, Liang, SS, Chow, NH & Shiue, YL 2015, 'The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma', Oncotarget, 卷 6, 編號 11, 頁 9220-9239. https://doi.org/10.18632/oncotarget.3312

The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma. / Li, Chien Feng; Wu, Wen Jeng; Wu, Wen Ren; Liao, Yu Jing; Chen, Lih Ren; Huang, Chun Nung; Li, Ching Chia; Li, Wei Ming; Huang, Hsuan Ying; Chen, Yi Ling; Liang, Shih Shin; Chow, Nan Haw; Shiue, Yow Ling.

於: Oncotarget, 卷 6, 編號 11, 01.01.2015, p. 9220-9239.

研究成果: Article

TY - JOUR

T1 - The cAMP responsive element binding protein 1 transactivates epithelial membrane protein 2, a potential tumor suppressor in the urinary bladder urothelial carcinoma

AU - Li, Chien Feng

AU - Wu, Wen Jeng

AU - Wu, Wen Ren

AU - Liao, Yu Jing

AU - Chen, Lih Ren

AU - Huang, Chun Nung

AU - Li, Ching Chia

AU - Li, Wei Ming

AU - Huang, Hsuan Ying

AU - Chen, Yi Ling

AU - Liang, Shih Shin

AU - Chow, Nan Haw

AU - Shiue, Yow Ling

PY - 2015/1/1

Y1 - 2015/1/1

N2 - In this study, we report that EMP2 plays a tumor suppressor role by inducing G2/M cell cycle arrest, suppressing cell viability, proliferation, colony formation/ anchorage-independent cell growth via regulation of G2/M checkpoints in distinct urinary bladder urothelial carcinoma (UBUC)-derived cell lines. Genistein treatment or exogenous expression of the cAMP responsive element binding protein 1 (CREB1) gene in different UBUC-derived cell lines induced EMP2 transcription and subsequent translation. Mutagenesis on either or both cAMP-responsive element(s) dramatically decreased the EMP2 promoter activity with, without genistein treatment or exogenous CREB1 expression, respectively. Significantly correlation between the EMP2 immunointensity and primary tumor, nodal status, histological grade, vascular invasion and mitotic activity was identified. Multivariate analysis further demonstrated that low EMP2 immunoexpression is an independent prognostic factor for poor disease-specific survival. Genistein treatments, knockdown of EMP2 gene and double knockdown of CREB1 and EMP2 genes significantly inhibited tumor growth and notably downregulated CREB1 and EMP2 protein levels in the mice xenograft models. Therefore, genistein induced CREB1 transcription, translation and upregulated pCREB1(S133) protein level. Afterward, pCREB1(S133) transactivated the tumor suppressor gene, EMP2, in vitro and in vivo. Our study identified a novel transcriptional target, which plays a tumor suppressor role, of CREB1.

AB - In this study, we report that EMP2 plays a tumor suppressor role by inducing G2/M cell cycle arrest, suppressing cell viability, proliferation, colony formation/ anchorage-independent cell growth via regulation of G2/M checkpoints in distinct urinary bladder urothelial carcinoma (UBUC)-derived cell lines. Genistein treatment or exogenous expression of the cAMP responsive element binding protein 1 (CREB1) gene in different UBUC-derived cell lines induced EMP2 transcription and subsequent translation. Mutagenesis on either or both cAMP-responsive element(s) dramatically decreased the EMP2 promoter activity with, without genistein treatment or exogenous CREB1 expression, respectively. Significantly correlation between the EMP2 immunointensity and primary tumor, nodal status, histological grade, vascular invasion and mitotic activity was identified. Multivariate analysis further demonstrated that low EMP2 immunoexpression is an independent prognostic factor for poor disease-specific survival. Genistein treatments, knockdown of EMP2 gene and double knockdown of CREB1 and EMP2 genes significantly inhibited tumor growth and notably downregulated CREB1 and EMP2 protein levels in the mice xenograft models. Therefore, genistein induced CREB1 transcription, translation and upregulated pCREB1(S133) protein level. Afterward, pCREB1(S133) transactivated the tumor suppressor gene, EMP2, in vitro and in vivo. Our study identified a novel transcriptional target, which plays a tumor suppressor role, of CREB1.

UR - http://www.scopus.com/inward/record.url?scp=84928714256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928714256&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.3312

DO - 10.18632/oncotarget.3312

M3 - Article

C2 - 25940704

AN - SCOPUS:84928714256

VL - 6

SP - 9220

EP - 9239

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 11

ER -