Cell cycle-dependent modulation of telomerase activity in tumor cells

被引:225
作者
Zhu, XL
Kumar, R
Mandal, M
Sharma, N
Sharma, HW
Dhingra, U
Sokoloski, JA
Hsiao, RS
Narayanan, R
机构
[1] HOFFMANN LA ROCHE INC,ROCHE RES CTR,DIV ONCOL,NUTLEY,NJ 07110
[2] PENN STATE UNIV,COLL MED,DEPT MED,HERSHEY,PA 17033
[3] PENN STATE UNIV,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033
[4] YALE UNIV,SCH MED,DEV THERAPEUT PROGRAM,CTR CANC,NEW HAVEN,CT 06510
[5] YALE UNIV,SCH MED,CTR CANC,DEPT PHARMACOL,NEW HAVEN,CT 06510
关键词
cancer; telomeres; G2M; ribonucleoprotein;
D O I
10.1073/pnas.93.12.6091
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Telomerase is a ribonucleoprotein complex that is thought to add telomeric repeats onto the ends of chromosomes during the replicative phase of the the cell cycle. We tested this hypothesis by arresting human tumor cell lines at different stages of the cell cycle. Induction of quiescence by serum deprivation did not affect telomerase activity. Cells arrested at the G(1)/S phase of the cell cycle showed similar levels of telomerase to asynchronous cultures; progression through the S phase was associated with increased telomerase activity. The highest level of telomerase activity was detected in S-phase cells. In contrast, cells arrested at G(2)/M phase of the cell cycle were almost devoid of telomerase activity. Diverse cell cycle blockers, including transforming growth factor beta 1 and cytotoxic agents, also caused inhibition of telomerase activity. These results establish a direct link between telomerase activity and progression through the cell cycle.
引用
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页码:6091 / 6095
页数:5
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