Investigation of the role of p53 in chemotherapy resistance of lung cancer cell lines.
BACKGROUND
p53 is a tumour suppressor gene, which is mutated in more than half of all tumours. Most chemotherapeutic drugs cause DNA damage, which is sensed by p53; the cell can then try to repair the damage or induce cell suicide. If the p53 machinery is defective, effective chemotherapy is made more difficult.


METHODS
Wild-type p53 was transfected into lung cancer cell lines with different p53 status. The transfected cells were tested for changes in sensitivity to a range of chemotherapeutic agents.


RESULTS
We observed only modest changes in the sensitivity to the chemotherapeutic agents adriamycin, taxol and carboplatin in the transfected cells lines. p53 protein was detected in a transfected clone of the cell line H1299, whose parent cells are p53 null. However, the protein did not accumulate after DNA damage, suggesting that this cell line utilises alternative pathways for responding to stress, and no longer has a functional p53 pathway.


CONCLUSIONS
The results suggest that introduction of wild-type p53 alone is not sufficient to substantially alter the sensitivity of a cell line to a given chemotherapeutic agent.
Breen
Laura
L
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. laura.breen@dcu.ie
Heenan
Mary
M
Amberger-Murphy
Verena
V
Clynes
Martin
M
D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel