Despite the substantial public health impact of prostate cancer, little is known about its etiology. The generally accepted risk factors for the development of prostate cancer are advanced age, familial predisposition and perhaps ethnicity. The exon 1 of the AR contains several polymorphic repeats; the most variable is a polymorphic CAG repeat, which encodes a polyglutamine (poly-Q) chain. The range of CAG repeat lengths is from 14 to 35 repeats in man and may vary somewhat with ethnicity and race. Because the length of the polymorphic CAG trinucleotide repeat is inversely correlated with the transactivation function of the AR in vitro, it has been proposed that men with shorter repeats will be at higher risk for prostate cancer.14 Several previous studies have shown that shorter CAG repeat length in AR NTD is associated with the occurrence of more aggressive prostate cancer, earlier age of onset and likelihood of recur-rence.15 However, one small study in a European population failed to support the association between CAG repeat length and prostate cancer risk.16 The role of CAG repeats in prostate needs to be determined more clearly. By crossing AR-97Q and AR-24Q transgene male mice with our ARKO female mice, we are generating the ARKO mice carrying only 97-Q and 24-Q transgenic AR to compare the effects of different poly-Q lengths on the development of the prostate gland. Further crossing to TRAMP mice will create ARKO TRAMP mice with different poly-Q AR transgenes. By studying the differences in carcinogenesis and tumor progression in these mice, we will determine the effect of poly-Q lengths on the prostate cancer in vivo.
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