Lack of cell cycle regulation of telomerase activity in human cells

被引:159
作者
Holt, SE [1 ]
Aisner, DL [1 ]
Shay, JW [1 ]
Wright, WE [1 ]
机构
[1] UNIV TEXAS,SW MED CTR,DEPT NEUROSCI & CELL BIOL,DALLAS,TX 75235
关键词
D O I
10.1073/pnas.94.20.10687
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
Conflicting reports have appeared concerning the cell cycle regulation of telomerase activity and its possible repression during quiescence and cell differentiation. We have reexamined these issues in an attempt to uncover the basis for the discrepancies. Variations in extracted telomerase activity during the cell cycle are not observed in cells sorted on the basis of DNA content. Variations are observed in cells synchronized using some biochemical cell cycle inhibitors, but only with those agents where cellular toxicity is evident, A progressive decline in telomerase activity is observed in cells whose growth rate is reduced from seven to eight population doublings per week to one to two doublings per week. Telomerase is largely absent in cells that truly exit the cell cycle and do not divide over the 7-day period, Although it is not necessary for all cell types to regulate telomerase in the same way, we conclude that in the immortal cultured cell lines examined, extracted telomerase activity does not change significantly during progression through the stages of the cell cycle. Telomerase activity generally correlates with growth rate and is repressed in cells that exit the cell cycle and become quiescent.
引用
收藏
页码:10687 / 10692
页数:6
相关论文
共 40 条
[1]  
Albanell J, 1996, CANCER RES, V56, P1503
[2]   TELOMERE LENGTH PREDICTS REPLICATIVE CAPACITY OF HUMAN FIBROBLASTS [J].
ALLSOPP, RC ;
VAZIRI, H ;
PATTERSON, C ;
GOLDSTEIN, S ;
YOUNGLAI, EV ;
FUTCHER, AB ;
GREIDER, CW ;
HARLEY, CB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) :10114-10118
[3]  
Bestilny LJ, 1996, CANCER RES, V56, P3796
[4]   TELOMERASE ACTIVITY IN NORMAL AND MALIGNANT HEMATOPOIETIC-CELLS [J].
BROCCOLI, D ;
YOUNG, JW ;
DELANGE, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) :9082-9086
[5]   TELOMERE ELONGATION IN IMMORTAL HUMAN-CELLS WITHOUT DETECTABLE TELOMERASE ACTIVITY [J].
BRYAN, TM ;
ENGLEZOU, A ;
GUPTA, J ;
BACCHETTI, S ;
REDDEL, RR .
EMBO JOURNAL, 1995, 14 (17) :4240-4248
[6]   TELOMERASE ACTIVITY IN NORMAL LEUKOCYTES AND IN HEMATOLOGIC MALIGNANCIES [J].
COUNTER, CM ;
GUPTA, J ;
HARLEY, CB ;
LEBER, B ;
BACCHETTI, S .
BLOOD, 1995, 85 (09) :2315-2320
[7]   TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY [J].
COUNTER, CM ;
AVILION, AA ;
LEFEUVRE, CE ;
STEWART, NG ;
GREIDER, CW ;
HARLEY, CB ;
BACCHETTI, S .
EMBO JOURNAL, 1992, 11 (05) :1921-1929
[8]   STRUCTURE AND VARIABILITY OF HUMAN-CHROMOSOME ENDS [J].
DELANGE, T ;
SHIUE, L ;
MYERS, RM ;
COX, DR ;
NAYLOR, SL ;
KILLERY, AM ;
VARMUS, HE .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (02) :518-527
[9]  
Faraoni I, 1997, CLIN CANCER RES, V3, P579
[10]  
Gollahon LS, 1996, ONCOGENE, V12, P715