Journal Article

Molecular classification of green tea catechin-sensitive and green tea catechin-resistant prostate cancer in the TRAMP mice model by quantitative real-time PCR gene profiling

Maurizio Scaltriti, Lucia Belloni, Andrea Caporali, Pierpaola Davalli, Daniel Remondini, Federica Rizzi, Serenella Astancolle, Arnaldo Corti and Saverio Bettuzzi

in Carcinogenesis

Volume 27, issue 5, pages 1047-1053
Published in print May 2006 | ISSN: 0143-3334
Published online November 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi287
Molecular classification of green tea catechin-sensitive and green tea catechin-resistant prostate cancer in the TRAMP mice model by quantitative real-time PCR gene profiling

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We previously found that human prostate cancer (CaP) progression is accompanied by differential expression of a panel of 8 informative genes, some of which are metabolically related. Gene profiling focused on this 8-gene pack by northern blot analysis in combination with standard clinical information provided reliable prognostic prediction of human CaP. For a better insight into the potential of this 8-gene signature in tumor detection/classification and therapeutic response, we determined, by qPCR, the expression of these informative genes in the TRAMP mice model of CaP progression. The 8-genes signature resulted effective in discriminating, by linear discriminant analysis (LDA), the prostate of wild type mice from transgenic TRAMP mice developing CaP (P < 0.0002). Since it is known that Green Tea Catechin (GTC) administration to TRAMP mice results in a substantial delay of CaP progression in 80% of the animals, while 20% remain unresponsive, we determined the 8-gene signature in the prostates of GTC-sensitive and GTC-resistant mice. LDA discriminated benign tissue from CaP (i.e. wild-type + chemoprevented, GTC-sensitive TRAMP mice, in which CaP progression was delayed, was discriminated from TRAMP mice + GTC-resistant TRAMP mice, in which CaP developed irrespective of GTC administration; P < 0.01). Moreover, GTC-sensitive TRAMP mice bearing CaP were discriminated from GTCs-resistant ones, (P = 0.0001). These results show that qPCR gene profiling, based on the signature of the 8-genes selected by us, could represent an appropriate means for studying the biological behavior of CaP, which may lead to identifying new tools of potential prognostic value, in that a molecular classification for the presence/absence of cancer and for discriminating GTCs-responsive from GTC-resistant CaP is provided.

Keywords: ADO or AdoMetDC, adenosylmethionine decarboxylase; CaP, prostate cancer; CLU, clusterin; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; Gas1, growth arrest specific gene 1; GTCs, green tea catechins; LDA, Linear Discriminant Analysis; OAZ, ornithine decarboxylase antizyme; ODC, ornithine decarboxylase; PIN, prostate intraepithelial neoplasia; qPCR, quantitative PCR; SSAT, spermidine/spermine N1-acetyltransferase

Journal Article.  5344 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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