Telomere loss, telomerase, and cancer

摘要

AbstractTelomeric DNA safeguards chromosomes from genetic damage and rearrangement. Normal somatic cells lose telomeric DNA with each division and during normal human aging. Immortal cancer cells typically express the enzyme telomerase, a ribonucleoprotein polymerase that adds new telomere repeats onto the chromosome ends. To study the role of telomerase in cancer cells, the RNA component of human telomerase (hTR) was recently cloned. HeLa cells expressing antisense hTR exhibited reduced telomerase activity, gradual loss of telomeric DNA, and cell death after 23–26 doublings. These results demonstrate that telomerase is a critical enzyme for the continued proliferation of metastatic tumor cells. Whereas telomere loss occurs in both normal and precancerous cells, telomere shortening with age can lead to genetic damage, which may underlie the age‐related increases in cancer rates. © 1995 Wiley‐Lis