Telomerase activity modulation in the prevention of prostate cancer.
Telomerase is a ribonucleoprotein that stabilizes chromosomes by maintaining their telomeric ends. Although telomerase is normally expressed in reproductive tissues, it is virtually absent in most normal somatic tissues. During carcinogenesis, cells activate telomerase to protect chromosomal ends from the telomere erosion that occurs with replication. Prevention of telomere loss by activation of telomerase allows for the cellular immortalization that is a characteristic of cancer cells. Recent studies have shown that genetic instability arising from critical telomere shortening is a mechanism through which cancer cells attain multiple genetic aberrations that characterize a malignant clone. Thus, the timing of telomerase activation during carcinogenesis is likely to play an important role in modulating the genetic instability that determines the malignant phenotype. Earlier activation of telomerase should minimize genetic aberrations in neoplastic cells and lead to less aggressive tumors, or may prevent carcinogenesis. In this article, we discuss recent data on telomerase expression in prostate cancer, propose a model that relates the dynamics of telomerase activation to the evolution of different prostatic malignancies, and discuss the potential application of telomerase activation as a strategy for the prevention of prostate cancer.
Kim
N W
NW
Geron Corporation, Menlo Park, California 94025, USA.
Hruszkewycz
A M
AM
D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011467:Prostate / Q000201:enzymology; D011470:Prostatic Hyperplasia / Q000201:enzymology; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000517:prevention & control; D012313:RNA; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000502:physiology; D013997:Time Factors
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase