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Role of telomerase in cellular proliferation and cancer
Author(s) -
Holt Shawn E.,
Shay Jerry W.
Publication year - 1999
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199907)180:1<10::aid-jcp2>3.0.co;2-d
Subject(s) - telomerase , telomere , telomerase reverse transcriptase , biology , cell growth , cell cycle , cell division , cancer cell , telomerase rna component , microbiology and biotechnology , cancer research , senescence , cell , cancer , genetics , dna , gene
Telomerase is a cellular reverse transcriptase that helps to provide genomic stability in highly proliferative normal, immortal, and tumor cells by maintaining the integrity of the chromosome ends, the telomeres. The activity of telomerase is associated with the majority of malignant human cancers. Telomerase or another mechanism for telomere maintenance is required for continuous tumor cell proliferation. Telomerase‐positive cells that exit the cell cycle via quiescence downregulate telomerase through a transcriptional repression pathway. In the case of cell cycle exit via terminal differentiation, proteolysis of telomerase may also be involved. In response to mitogenic or growth factor signaling, telomerase‐competent quiescent cells reenter the cell cycle and express telomerase activity independent of DNA synthesis. Under normal growth conditions, inhibition of telomerase activity in tumor‐derived cells results in continued cell division coupled with telomere shortening, eventually followed by cellular senescence or death. Thus, repression of telomerase activity may be a novel adjuvant therapy for the treatment of human cancer and detection of telomerase activity may be important for cancer diagnostics. J. Cell. Physiol. 180:10–18, 1999. © 1999 Wiley‐Liss, Inc.