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.
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.
Scaltriti
Maurizio
M
Dipartimento di Medicina Sperimentale, Plesso Biotecnologico Integrato, Universita' di Parma, Via Volturno 39-43100 Parma, Italy.
Belloni
Lucia
L
Caporali
Andrea
A
Davalli
Pierpaola
P
Remondini
Daniel
D
Rizzi
Federica
F
Astancolle
Serenella
S
Corti
Arnaldo
A
Bettuzzi
Saverio
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002392:Catechin / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D013662:Tea
D016588:Anticarcinogenic Agents; D017931:DNA Primers; D013662:Tea; D002392:Catechin