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Titolo:
EFFECT OF ONCOGENE EXPRESSION ON TELOMERASE ACTIVATION AND TELOMERE LENGTH IN HUMAN ENDOTHELIAL, FIBROBLAST AND PROSTATE EPITHELIAL-CELLS
Autore:
BURGER AM; FIEBIG HH; KUETTEL MR; LAUTENBERGER JA; KUNG HF; RHIM JS;
Indirizzi:
NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL FREDERICK MD 21702 NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL FREDERICK MD 21702 UNIV FREIBURG,TUMOR BIOL CTR D-79106 FREIBURG GERMANY GEORGETOWN UNIV,SCH MED,VINCENT T LOMBARDI CANC RES CTR,DEPT RADIAT MED WASHINGTON DC 00000
Titolo Testata:
International journal of oncology
fascicolo: 5, volume: 13, anno: 1998,
pagine: 1043 - 1048
SICI:
1019-6439(1998)13:5<1043:EOOEOT>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
V-KI-RAS; NEOPLASTIC TRANSFORMATION; CANCER; IMMORTALIZATION; TRANSFECTION; PLASMID;
Keywords:
TELOMERASE ACTIVITY; TELOMERES; E6; E7; V-KI-RAS; HUVEC; FIBROBLASTS; BENIGN PROSTATE HYPERPLASIA PROSTATE EPITHELIAL CELLS; TUMORIGENICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
A.M. Burger et al., "EFFECT OF ONCOGENE EXPRESSION ON TELOMERASE ACTIVATION AND TELOMERE LENGTH IN HUMAN ENDOTHELIAL, FIBROBLAST AND PROSTATE EPITHELIAL-CELLS", International journal of oncology, 13(5), 1998, pp. 1043-1048

Abstract

Although strong evidence is mounting that telomerase reactivation andthe thereof resulting stabilization of telomeres is a major mechanismfor human cells to overcome replicative senescence, a causal relationship linking telomerase activation conclusively to tumorigenesis remains to be established. Thus, the possibility exists that telomerase activation is passively co-selected as tumors develop. To elucidate the function of telomerase during tumorigenesis, we followed telomerase reactivation during immortalization of human primary cell types with in vitro transforming agents and determined the tumorigenic potential of these cells at various stages of transformation. The effects of SV40, v-Ki-ms, HPV-18 and HPV-16 E6/E7 oncoproteins on telomerase expression was examined in primary and immortalized human prostate epithelial (HPE), human prostate fibroblast (HPF), and umbilical vein endothelial cells (HUVEC). All of five SV40-transformed HPE and HPF lines were telomerase positive and had shorter telomeres than primary cells. The two HPV-18 immortalized HPE cell lines also expressed telomerase activity. In contrast, EG or E7 alone could not produce immortalized HUVEC and did not reactivate telomerase. Life-span, however, was extended. The E6/E7 immortalized HUVEC had telomerase activity and short but stable telomeres. HPE, HPF or HUVEC cells which had been transformed by one oncoprotein alone were not tumorigenic although they had overcome cellular senescence and reactivated telomerase. However, if these cells were transformed by a second agent, either infection with v-Ki-ras or X-raytreatment, they were able to form tumors in nude mice. This suggests that tumorigenesis is a multistep process and that telomerase activation alone is not sufficient for malignant transformation in human cells.

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Documento generato il 27/01/20 alle ore 07:25:36