Medical College of Wisconsin
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SmgGDS is up-regulated in prostate carcinoma and promotes tumour phenotypes in prostate cancer cells. J Pathol 2009 Feb;217(3):389-97

Date

11/01/2008

Pubmed ID

18973191

DOI

10.1002/path.2456

Scopus ID

2-s2.0-60549096862 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

SmgGDS is a guanine nucleotide exchange factor with the unique ability to activate multiple small GTPases, implicating it in cancer development and progression. Here, we investigated the role of SmgGDS in prostate cancer by studying the expression of SmgGDS in benign and malignant prostatic tissues. We also probed SmgGDS function in three prostate carcinoma cell lines using small interfering RNA (siRNA). Immunohistochemical analysis revealed that SmgGDS levels were elevated in prostatic intraepithelial neoplasia (PIN), prostate carcinoma, and metastatic prostate carcinoma. In addition, expression of SmgGDS positively correlated with that of cyclooxygenase-2 (COX-2), a protein believed to promote the development of prostate carcinoma. Reduction of SmgGDS expression in prostate carcinoma cells inhibited proliferation and migration, irrespective of androgen receptor status. These effects were accompanied by a reduction in COX-2 expression and in activity of NF-kappaB, a known regulator of COX-2. Taken together, these findings suggest that SmgGDS promotes the development and progression of prostate cancer, possibly associated with NF-kappaB-dependent up-regulation of COX-2.

Author List

Zhi H, Yang XJ, Kuhnmuench J, Berg T, Thill R, Yang H, See WA, Becker CG, Williams CL, Li R

Author

Carol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Carcinoma
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cyclooxygenase 2
Gene Expression Regulation, Neoplastic
Guanine Nucleotide Exchange Factors
Humans
Immunohistochemistry
Male
NF-kappa B
Prostate
Prostatic Neoplasms
RNA, Small Interfering
Tissue Array Analysis
Transcription, Genetic
Transfection
Up-Regulation