RGD Reference Report - Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. - Rat Genome Database

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

Authors: Lu, S  Lee, J  Revelo, M  Wang, X  Lu, S  Dong, Z 
Citation: Lu S, etal., Clin Cancer Res. 2007 Oct 1;13(19):5692-702.
RGD ID: 2300396
Pubmed: PMID:17908958   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-07-1078   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SMAD3Humanprostate cancer disease_progressionIEP protein:increased expression:tumor:significantly elevated in 53/67 (79%, p=0.0002) overall more ...RGD 
Smad3Ratprostate cancer disease_progressionISOSMAD3 (Homo sapiens) RGD 
Smad3Mouseprostate cancer disease_progressionISOSMAD3 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Smad3  (SMAD family member 3)

Genes (Mus musculus)
Smad3  (SMAD family member 3)

Genes (Homo sapiens)
SMAD3  (SMAD family member 3)


Additional Information