Telomeres, telomerase, and telomerase inhibition: Clinical implications for cancer

被引:26
作者
Ahmed, A
Tollefsbol, T
机构
[1] Univ Alabama Birmingham, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Birmingham, AL USA
[2] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Birmingham, AL USA
[3] Univ Alabama Birmingham, Ctr Outcomes & Effectiveness Res & Educ, Ctr Aging, Birmingham, AL USA
[4] Univ Alabama Birmingham, Ctr Metab & Bone Dis, Birmingham, AL USA
[5] VA Med Ctr, Heart Failure Clin, Birmingham, AL USA
[6] VA Med Ctr, Sect Geriatr, Birmingham, AL USA
[7] Univ Alabama Birmingham, Sch Nat Sci & Math, Dept Biol, Birmingham, AL USA
[8] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA
关键词
cancer; telomeres; telomerase; telomerase inhibition;
D O I
10.1034/j.1601-5215.2002.51019.x
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Telomeres are located at the ends of eukaryotic chromosomes. The enzyme telomerase synthesized them, and they are responsible for maintaining the lengths of chromosomes. Absence of telomerase is associated with telomere shortening and aging of somatic cells, but high telomerase activity is observed in over 90% of human cancer cells. Although the disappearance of telomerase with aging is considered a natural defense against development of cancer, it is not known what triggers the reappearance of telomerase in cancer cells. Telomerase activity is directly correlated with the expression of its active catalytic component, the human telomerase reverse transcriptase (hTERT), which is controlled primarily at the level of transcription. An earlier paper discussed the relationship of telomerase with aging. In this article, the contemporary literature is reviewed to explore the associations between telomerase, telomerase inhibition, and cancer. Because most cancers occur in old age, with the aging of the population, the number of people suffering from cancer is expected to increase in the coming decades. It is not known what roles telomerase and hTERT play in the complex relationship between aging and cancer. Data from experimental studies suggest that telomerase assay could potentially play a role in the diagnosis and prognosis of cancers. There is also evidence that telomerase inhibitors might be used as anticancer agents. As the knowledge of the relationships between telomerase and cancer and between telomerase and aging advances, it is hoped that more about the interacting relationships between telomerase, aging, and cancer will be learned.
引用
收藏
页码:116 / 122
页数:7
相关论文
共 104 条
[1]   Telomeres and telomerase: Basic science implications for aging [J].
Ahmed, A ;
Tollefsbol, T .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 2001, 49 (08) :1105-1109
[2]  
Aogi K, 1998, CLIN CANCER RES, V4, P1965
[3]  
Arai T, 1998, ONCOL REP, V5, P405
[4]   Expression of human telomerase subunit genes in primary lung cancer and its clinical significance [J].
Arinaga, M ;
Shimizu, S ;
Gotoh, K ;
Haruki, N ;
Takahashi, T ;
Takahashi, T ;
Mitsudomi, T .
ANNALS OF THORACIC SURGERY, 2000, 70 (02) :401-405
[5]  
Balducci L, 1997, CLIN GERIATR MED, V13, P1
[6]  
Bednarek AK, 1997, CLIN CANCER RES, V3, P11
[7]   Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [J].
Blasco, MA ;
Lee, HW ;
Hande, MP ;
Samper, E ;
Lansdorp, PM ;
DePinho, RA ;
Greider, CW .
CELL, 1997, 91 (01) :25-34
[8]   Extension of life-span by introduction of telomerase into normal human cells [J].
Bodnar, AG ;
Ouellette, M ;
Frolkis, M ;
Holt, SE ;
Chiu, CP ;
Morin, GB ;
Harley, CB ;
Shay, JW ;
Lichtsteiner, S ;
Wright, WE .
SCIENCE, 1998, 279 (5349) :349-352
[9]   High telomerase activity is associated with cell cycle deregulation and rapid progression in endometrioid adenocarcinoma of the uterus [J].
Bonatz, G ;
Frahm, SO ;
Klapper, W ;
Helfenstein, A ;
Heidorn, K ;
Jonat, W ;
Krupp, G ;
Parwaresch, R ;
Rudolph, P .
HUMAN PATHOLOGY, 2001, 32 (06) :605-614
[10]   DISEASES AND DISORDERS OF AGING - AN HYPOTHESIS [J].
BRODY, JA ;
SCHNEIDER, EL .
JOURNAL OF CHRONIC DISEASES, 1986, 39 (11) :871-876