Experimental elongation of telomeres extends the lifespan of immortal x normal cell hybrids

被引:131
作者
Wright, WE
Brasiskyte, D
Piatyszek, MA
Shay, JW
机构
[1] Univ. Texas Southwestern Med. C., Dept. of Cell Biol. and Neurosci., Dallas, TX 75235-9039
关键词
aging; cancer; cell hybrids; telomerase; telomeres;
D O I
10.1002/j.1460-2075.1996.tb00519.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hybrids between immortal cells that express telomerase and normal cells that lack telomerase have a limited lifespan. We demonstrate that telomerase is repressed in such hybrids. Treatment of immortal human cell lines with certain oligonucleotides resulted in telomere elongation. We took advantage of this observation to test the hypothesis that elongation of telomeres would extend the lifespan of cells in culture. An immortal human cell line was treated with an oligonucleotide to lengthen its telomeres and then was fused with mortal cells. The lifespan of these hybrid cells was longer than that of the hybrids in which telomeres had not been elongated. These observations provide the first direct evidence supporting the hypothesis that telomere length determines proliferative capacity of human cells.
引用
收藏
页码:1734 / 1741
页数:8
相关论文
共 66 条
  • [1] TELOMERE LENGTH PREDICTS REPLICATIVE CAPACITY OF HUMAN FIBROBLASTS
    ALLSOPP, RC
    VAZIRI, H
    PATTERSON, C
    GOLDSTEIN, S
    YOUNGLAI, EV
    FUTCHER, AB
    GREIDER, CW
    HARLEY, CB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) : 10114 - 10118
  • [2] ASSIGNMENT OF 2 HUMAN EPIDERMAL SQUAMOUS-CELL CARCINOMA CELL-LINES TO MORE THAN ONE COMPLEMENTATION GROUP FOR THE IMMORTAL PHENOTYPE
    BERRY, IJ
    BURNS, JE
    PARKINSON, EK
    [J]. MOLECULAR CARCINOGENESIS, 1994, 9 (03) : 134 - 142
  • [3] TELOMERASES
    BLACKBURN, EH
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1992, 61 : 113 - 129
  • [4] FUNCTIONAL-CHARACTERIZATION AND DEVELOPMENTAL REGULATION OF MOUSE TELOMERASE RNA
    BLASCO, MA
    FUNK, W
    VILLEPONTEAU, B
    GREIDER, CW
    [J]. SCIENCE, 1995, 269 (5228) : 1267 - 1270
  • [5] TELOMERASE ACTIVITY IN NORMAL AND MALIGNANT HEMATOPOIETIC-CELLS
    BROCCOLI, D
    YOUNG, JW
    DELANGE, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (20) : 9082 - 9086
  • [6] TELOMERE ELONGATION IN IMMORTAL HUMAN-CELLS WITHOUT DETECTABLE TELOMERASE ACTIVITY
    BRYAN, TM
    ENGLEZOU, A
    GUPTA, J
    BACCHETTI, S
    REDDEL, RR
    [J]. EMBO JOURNAL, 1995, 14 (17) : 4240 - 4248
  • [7] LIMITED LIFESPAN IN SOMATIC-CELL HYBRIDS AND CYBRIDS
    BUNN, CL
    TARRANT, GM
    [J]. EXPERIMENTAL CELL RESEARCH, 1980, 127 (02) : 385 - 396
  • [8] CHADENEAU C, 1995, CANCER RES, V55, P2533
  • [9] TELOMERASE ACTIVITY IN HUMAN OVARIAN-CARCINOMA
    COUNTER, CM
    HIRTE, HW
    BACCHETTI, S
    HARLEY, CB
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) : 2900 - 2904
  • [10] TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY
    COUNTER, CM
    AVILION, AA
    LEFEUVRE, CE
    STEWART, NG
    GREIDER, CW
    HARLEY, CB
    BACCHETTI, S
    [J]. EMBO JOURNAL, 1992, 11 (05) : 1921 - 1929