TY - JOUR
T1 - Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes
AU - Argilla, David
AU - Chin, Koei
AU - Singh, Mallika
AU - Hodgson, J. Graeme
AU - Bosenberg, Marcus
AU - De Solórzano, Carlos Ortiz
AU - Lockett, Stephen
AU - DePinho, Ronald A.
AU - Gray, Joe
AU - Hanahan, Douglas
N1 - Funding Information:
We thank Michael Rizen for initiating the breeding to establish the terc −/− allele in the transgenic mouse backgrounds, Nicole Meyer-Morse for assistance, Monica Miranda for assistance in FISH experiments, Carol Greider for advice and encouragement during the early stages of this project, Titia de Lange and John Murnane for suggestions and encouragement, Kwok-Kin Wong for comments on the manuscript, and Martha Stamper and Paul Yaswen for providing the HMEC lines. This work was supported by grants from the National Cancer Institute.
PY - 2004/10
Y1 - 2004/10
N2 - The telomere-stabilizing enzyme telomerase is induced in tumors and functionally associated with unlimited replicative potential. To further explore its necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit carcinomas in pancreas and skin, respectively, were rendered telomerase-deficient. Absence of telomerase had minimal impact on tumorigenesis, even in terc-/- generations (G5-7) exhibiting shortened telomeres and phenotypic abnormalities in multiple organs. Analyses of chromosomal aberrations were not indicative of telomere dysfunction or increased genomic instability in tumors. Quantitative image analysis of telomere repeat intensities comparing biopsies of skin hyperplasia, dysplasia, and carcinoma revealed that telomere numbers and relative lengths were maintained during progression, implicating a means for preserving telomere repeats and functionality in the absence of telomerase.
AB - The telomere-stabilizing enzyme telomerase is induced in tumors and functionally associated with unlimited replicative potential. To further explore its necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit carcinomas in pancreas and skin, respectively, were rendered telomerase-deficient. Absence of telomerase had minimal impact on tumorigenesis, even in terc-/- generations (G5-7) exhibiting shortened telomeres and phenotypic abnormalities in multiple organs. Analyses of chromosomal aberrations were not indicative of telomere dysfunction or increased genomic instability in tumors. Quantitative image analysis of telomere repeat intensities comparing biopsies of skin hyperplasia, dysplasia, and carcinoma revealed that telomere numbers and relative lengths were maintained during progression, implicating a means for preserving telomere repeats and functionality in the absence of telomerase.
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U2 - 10.1016/j.ccr.2004.08.032
DO - 10.1016/j.ccr.2004.08.032
M3 - Article
C2 - 15488760
AN - SCOPUS:5444249348
SN - 1535-6108
VL - 6
SP - 373
EP - 385
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -