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

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-genes 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-genes 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 Catechins (GTCs) 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-genes signature in the prostates of GTCs-sensitive and GTCs-resistant mice. LDA discriminated benign tissue from CaP (i.e. wild type + chemoprevented, GTCs-sensitive TRAMP mice, in which CaP progression was delayed, was discriminated from TRAMP mice + GTCs-resistant TRAMP mice, in which CaP developed irrespectively from GTCs administration; p < 0.01). Moreover, GTCs-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 presence/absence of cancer and for discriminating GTCs-responsive from GTCs-resistant CaPs is provided.