Telomerase activity in human ovarian carcinoma.

Abstract

Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid In chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintaine in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findilgs suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.Telomeres contain both DNA and protein that together appear to stabilize the ends ofeukaryotic DNA (reviewed in refs.

Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

“…Moreover, if telomere damage does play a role in triggering cell cycle arrest, one should expect the ability of a cell to maintain its telomeres to be important for the duration and/or severity of the arrest. While most somatic human cells cannot counteract telomere shortening, immortal cells, among them at least 85% of all tumor cells, do have this possibility mostly by activation of the telomere-elongating enzyme: telomerase (Counter et al, 1994;Shay and Bacchetti, 1997).…”

Human cord blood-derived primitive progenitors are enriched in CD34+c-kit− cells: correlation between long-term culture-initiating cells and telomerase expression

“…2,6 Since telomerase activity is absent in most somatic cells, telomere shortening occurs in these cells. [7][8][9][10] In contrast, immortal tumor cell lines and germ cell tissues show high levels of telomerase activity, resulting in a stable telomere length and unlimited proliferation. 7,11 It was recently reported that human hematopoietic stem/progenitor cells and activated lymphocytes exhibit low levels of telomerase activity.…”

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

“…More recently, the enzyme telomerase has been attracting interest as another promising candidate marker (Counter et al, 1994). The 'telomere hypothesis' proposes that activation of telomerase is necessary for cells to become immortal or capable of extended proliferation (Rhyu, 1995;Shay et al, 1995).…”