Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice.

Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. Research Abstract Details 

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Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. Abstract Text:

Shan Lu,Juwon Lee,Monica Revelo,Xiaohong Wang,Shan Lu,Zhongyun Dong,Shan Lu,Juwon Lee,Monica Revelo,Xiaohong Wang,Shan Lu,Zhongyun Dong,

PURPOSE: The purpose of this study was to investigate the potential role of Smad3, a key mediator of transforming growth factor-beta signaling, in progression of prostate cancer. EXPERIMENTAL DESIGN: Expression of Smad proteins was determined in human prostate cancer tissue array and cell lines. Growth and metastasis of cells overexpressing dominant-negative Smad3 (Smad3D) were studied to determine its role in tumor progression in mice. Cell growth, apoptosis, and expression of angiogenic molecules in tumor lesions were studied to determine potential pathways that Smad3 promotes tumor progression. RESULTS: Smad3 was overexpressed in human prostate cancer, which correlated with Gleason score and expression of proliferating cell nuclear antigen. Androgen-independent PC-3MM2 and DU145 cells expressed much higher levels of Smad3 than did androgen-dependent LNCaP, 22Rv1, and LAPC-4 cells. Overexpression of Smad3D in PC-3MM2 cells (PC-3MM2-Smad3D) had minimal direct effects on cell growth but attenuated effects of transforming growth factor-beta1 on gene expression and cell growth. Overexpression of Smad3D did not significantly alter tumor incidence but reduced tumor growth rate and metastasis incidence. Most cells in the control tumors, but not PC-3MM2-Smad3D tumors, were positively stained by an antibody to proliferating cell nuclear antigen. Microvessels and expression of angiogenic molecule interleukin-8 were significantly reduced in tumors from PC-3MM2-Smad3D cells. PC-3MM2-Smad3D tumors also expressed lower levels of vascular endothelial growth factor and platelet-derived growth factor. CONCLUSIONS: These data suggest that Smad3, through regulating angiogenic molecule expression in tumor cells, is critical for progression of human prostate cancer.

Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. Publishing Authors By Initials

S Lu,J Lee,M Revelo,X Wang,S Lu,Z Dong,S Lu,J Lee,M Revelo,X Wang,S Lu,Z Dong,

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Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 5692-702

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Oct

YEAR: 2007

Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

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Grant and Affiliation Information for Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice.

AFFILIATION: Department of Internal Medicine, The University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA97099-01A1

ACRONYM: CA

MEDLINETA: Clin Cancer Res

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