Multiple factors contribute to the development of prostate carcinoma (PCa) and to its progression to an androgen-independent state. In addition to the expected role of androgens and their receptors in facilitating the development of PCa, mutations in a growing number of candidate hereditary prostate cancer loci and genes, such as RNASEL and MSR1, have been detected, suggesting that defects in critical pathways involving DNA damage response, apoptosis and innate immunity may have a particularly important role in the initiation of PCa. Many somatic mutations, gene deletions, gene amplifications, chromosomal rearrangements, and changes in DNA methylation are detectable in PCa cells at the time of diagnosis. The identification of key molecular alteration cells implicates carcinogen defenses, including GSTP1, growth factor signaling pathways (such as PTEN and p27) and androgens as critical determinants of the phenotype of PCa.
Copyright 2004 Springer-Verlag