Community Research and Development Information Service - CORDIS

FP5

IMPALED Report Summary

Project ID: QLK3-CT-2002-01956
Funded under: FP5-LIFE QUALITY
Country: Sweden

Assessment of the role of mitochondria in resistance of lung cancer cells to treatment

Impaired radiotherapy response in NSCLC is clinical problem leading to improper tumour control. We have found that defective signalling from the initial DNA damage to induction of apoptosis is one contributing factor. Thus we have shown that in a NSCLC cell line defective activation of the pro-apoptotic proteins Bak and Bax as well as impeded activation of the stress-activated protein kinases JNK and p38 contribute to apoptotic resistance to low-LET? -Radiation.

Irradiation using high Linear Energy Transfer (high-LET) i.e., accelerated ions or radioactive nucleotides emitting? -Particles give rise to more complex DNA-strand breaks compared to low-LET? -Radiation and are currently evaluated for clinical use.

We have found that increased apoptotic signalling results from high-LET radiation in NSCLC cells compared to Low-LET radiation suggesting that high-LET radiation might have improved efficacy.

Moreover, we report that high and low-LET radiation likely differ in their way to activate the pro-apoptotic Bcl-2 family members Bak and Bax as well as the stress-activated protein kinase (SAPK) c-jun N-terminal kinases (JNK). Potential users of this knowledge is pharmaceutical industries developing DNA damaging sensitizing drugs as well as researches which analyze radio resistance mechanisms or explore cellular responses to different radiation qualities.

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Contact

Rolf LEWENSOHN, (Research Director)
Tel.: +46-851773188
Fax: +46-851775042
E-mail
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