Radiation-induced changes of telomerase activity in a human Ewing xenograft tumor.
OBJECTIVE
The effect of ionizing irradiation on telomerase activity and further associated biological factors was evaluated in a human Ewing tumor xenograft model on nude mice.


METHODS
The human Ewing tumor cell line STA-ET-1 was established in a nude mouse model. Initially, the dose-response relationship for the tumor model was established. For the radiation experiments two dose levels were chosen: 5 Gy and 30 Gy. After 5 Gy, there was no significant growth delay whereas after 30 Gy there was a marked growth delay without the induction of a complete remission. Tumors were examined 6, 12, 24, 48, 72, and 96 hours post irradiation. After irradiation with 30 Gy further time points were 6, 9, 12 and 15 days. For each dose and time group, three tumors were evaluated.


RESULTS
There was a reduction of telomerase activity after 5 Gy to 50% (not statistically significant) after 3 days; however, after 30 Gy there was a reduction of telomerase activity to 23% of the initial value after 6 days (p = 0.001). Telomerase activity correlated with the expression of human telomerase reverse transcriptase (hTERT), but not with the expression of telomerase-associated protein (TP1) and human telomerase RNA (hTR). The maximal amounts of necrosis or apoptosis after 30 Gy were 19% and 6.9%, respectively.


CONCLUSIONS
Ionizing radiation reduces telomerase activity and the expression of hTERT which cannot be explained by the induction of necrosis or apoptosis alone. The reduction of telomerase activity may contribute to delayed cell death after radiotherapy. The combined use of radiation and specific telomerase inhibitors may be a potentially synergistic treatment strategy.
Schuck
Andreas
A
Department of Radiotherapy, University Clinic of Muenster, Germany. schuck@uni-muenster.de
Poremba
Christopher
C
Lanvers
Claudia
C
Könemann
Stefan
S
Schleifer
Tobias
T
Wai
Daniel
D
Horn
Kirsten
K
Hesselmann
Stefan
S
Braun
Yvonne
Y
Frodermann
Bernd
B
Schäfer
Karl-Ludwig
KL
Diallo
Raihanatou I
RI
Rübe
Claudia E
CE
Rübe
Christian
C
Dockhorn-Dworniczak
Barbara
B
Willich
Normann
N
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D010315:Particle Accelerators; D012512:Sarcoma, Ewing / Q000473:pathology / Q000532:radiotherapy*; D019098:Telomerase / Q000528:radiation effects*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D019098:Telomerase