Telomeres and telomerase in prostatic intraepithelial neoplasia and prostate cancer biology.
Telomeres are terminal, repeated deoxyribonucleic acid (DNA) sequences that stabilize and protect the ends of the chromosomes. Mounting evidence indicates that by initiating chromosomal instability, short dysfunctional telomeres may be involved in prostate carcinogenesis. Although the exact cause of the telomere shortening observed in prostate cancer remains a mystery, telomere loss is known to occur during cell division and oxidative DNA damage, 2 byproducts of chronic inflammation, which is a common histologic finding in the prostate. In addition to prostate cancer causation, telomeres may also play a role in disease progression, and there are indications that tumor telomere content may prove useful as a prognostic marker. Once established, prostate cancer cells almost invariably activate the telomeric DNA polymerase enzyme telomerase, the detection of which may prove useful for diagnostic purposes. Interestingly, telomerase activity is suppressed in prostate cancer cells after androgen withdrawal, raising the possibility that androgen ablative therapies may re-instigate telomere loss, and consequent genetic instability, in surviving cancer cells, thus contributing to the emergence of an androgen-independent, lethal phenotype. A more thorough understanding of telomere biology as it relates to prostate cancer should provide new opportunities for disease prevention, diagnosis, prognostication, and treatment.
Meeker
Alan K
AK
Department of Pathology, Division of Genitourinary Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231-1000, USA. ameeker@mail.jhmi.edu
D006801:Humans; D008297:Male; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000209:etiology*; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000502:physiology*
D019098:Telomerase