Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes.
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.
Department of Biochemistry and Biophysics, Diabetes Center, and Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
David
D
Argilla
Koei
K
Chin
Mallika
M
Singh
J Graeme
JG
Hodgson
Marcus
M
Bosenberg
Carlos Ortiz
CO
de Solórzano
Stephen
S
Lockett
Ronald A
RA
DePinho
Joe
J
Gray
Douglas
D
Hanahan
D000705:Anaphase; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D043171:Chromosomal Instability; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D006824:Hybridization, Genetic; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D018345:Mice, Knockout; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D019098:Telomerase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
D009856:Oncogene Proteins, Viral; D019098:Telomerase