U94 alters FN1 and ANGPTL4 gene expression and inhibits tumorigenesis of prostate cancer cell line PC3Reportar como inadecuado




U94 alters FN1 and ANGPTL4 gene expression and inhibits tumorigenesis of prostate cancer cell line PC3 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cancer Cell International

, 5:19

First Online: 22 June 2005Received: 13 May 2004Accepted: 22 June 2005

Abstract

BackgroundInsensitivity of advanced-stage prostate cancer to androgen ablation therapy is a serious problem in clinical practice because it is associated with aggressive progression and poor prognosis. Targeted therapeutic drug discovery efforts are thwarted by lack of adequate knowledge of genes associated with prostate tumorigenesis. Therefore there is the need for studies to provide leads to targeted intervention measures. Here we propose that stable expression of U94, a tumor suppressor gene encoded by human herpesvirus 6A HHV-6A, could alter gene expression and thereby inhibit the tumorigenicity of PC3 cell line. Microarray gene expression profiling on U94 recombinant PC3 cell line could reveal genes that would elucidate prostate cancer biology, and hopefully identify potential therapeutic targets.

ResultsWe have shown that stable expression of U94 gene in PC3 cell line inhibited its focus formation in culture, and tumorigenesis in nude mice. Moreover gene expression profiling revealed dramatic upregulation of FN 1 fibronectin, 91 ± 16-fold, and profound downregulation of ANGPTL 4 angiopoietin-like-4, 20 ± 4-fold in U94 recombinant PC3 cell line. Quantitative real-time polymerase chain reaction QRT-PCR analysis showed that the pattern of expression of FN 1 and ANGPTL 4 mRNA were consistent with the microarray data. Based on previous reports, the findings in this study implicate upregulation of FN 1 and downregulation of ANGPTL 4 in the anti tumor activity of U94. Genes with cancer inhibitory activities that were also upregulated include SERPINE 2 serine-cysteine protease inhibitor 2, 7 ± 1-fold increase and ADAMTS 1 a disintegrin-like and metalloprotease with thrombospondin type 1 motif, 7 ± 2-fold increase. Additionally, SPUVE 23 serine protease 23 that is pro-tumorigenic was significantly downregulated 10 ± 1-fold.

ConclusionThe dramatic upregulation of FN 1 and downregulation of ANGPTL 4 genes in PC3 cell line stably expressing U94 implicate up-regulation of FN 1 and downregulation of ANGPTL 4 in anti tumor activity of U94. Further studies are necessary to determine functional roles of differentially expressed genes in U94 recombinant PC3 cell line, and hopefully provide leads to potential therapeutic targets in prostate cancer.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2867-5-19 contains supplementary material, which is available to authorized users.

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Autor: Ekwere T Ifon - Alan LY Pang - Warren Johnson - Kathleen Cashman - Sharon Zimmerman - Sumitra Muralidhar - Wai-Yee Chan -

Fuente: https://link.springer.com/







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