Telomere shortening and tumor formation by mouse cells lacking telomerase RNA

被引：1783

作者：

Blasco, MA

Lee, HW

Hande, MP

Samper, E

Lansdorp, PM

DePinho, RA

Greider, CW

机构：

[1] COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724

[2] YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10461

[3] UNIV AUTONOMA MADRID,DEPT IMMUNOL & ONCOL,CTR NACL BIOTECNOL,CSIC,E-28049 MADRID,SPAIN

[4] BRITISH COLUMBIA CANC RES CTR,TERRY FOX LAB,VANCOUVER,BC V5Z 1L3,CANADA

[5] UNIV BRITISH COLUMBIA,DEPT MED,VANCOUVER,BC V5Z 1M9,CANADA

来源：

CELL | 1997年 / 91卷 / 01期

关键词：

D O I：

10.1016/S0092-8674(01)80006-4

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：

To examine the role of telomerase in normal and neoplastic growth, the telomerase RNA component (mTR) was deleted from the mouse germline. mTR(-/-) mice lacked detectable telomerase activity yet were viable for the six generations analyzed. Telomerase-deficient cells could be immortalized in culture, transformed by viral oncogenes, and generated tumors in nude mice following transformation. Telomeres were shown to shorten at a rate of 4.8 +/- 2.4 kb per mTR(-/-) generation. Cells from the fourth mTR(-/-) generation onward possessed chromosome ends lacking detectable telomere repeats, aneuploidy, and chromosomal abnormalities, including end-to-end fusions. These results indicate that telomerase is essential for telomere length maintenance but is not required for establishment of cell lines, oncogenic transformation, or tumor formation in mice.

引用

页码：25 / 34

页数：10

共 53 条

[21]

Harley C.B., 1990, METHOD MOL BIOL, P25

[22] TELOMERASE, CELL IMMORTALITY, AND CANCER [J].