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Multidrug resistance related genes and p53 expression in human non small cell lung cancer
S Galimberti1, A Marchetti, F Buttitta
1Oncology Department, University of Pisa, Italy.
Background:
Many genes (mdr1, mrp, DNA topoisomerases II) are known to be involved in the resistance to unrelated drugs (the MDR phenomenon), but the mechanisms of their activation have to be further investigated.
Materials And Methods:
Because several authors showed that p53 mutated gene was able to induce mdr1 overexpression, we evaluated in 51 non small cell lung cancer samples, already tested for p53 mutations, the expression of mdr1, mrp, DNA topoisomerase II alpha and beta mRNAs by qualitative RT-PCR assays.
Results:
Mutations of p53 were found in 56% of cases. Mdr1 expression was detected in 27%, mrp in 100%, topoisomerase alpha in 82% and beta in 94% of the samples.
Conclusions:
It was not possible to detect any relationship between the expression of the MDR-related genes and tumor histological type, stage or lymph node involvement. Nevertheless, a close association between p53 alterations and either mdr1 gene (p = 0.001) or DNA topoisomerase II alpha (p = 0.003) expression was found.
Insights
p53 gene alterations are closely associated with the expression of mdr1 and DNA topoisomerase II alpha in non-small cell lung cancer. This finding helps understand multidrug resistance (MDR) mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) involves genes like mdr1, mrp, and DNA topoisomerases II.
- Mechanisms of MDR gene activation require further investigation.
Purpose of the Study:
- To investigate the relationship between p53 mutations and the expression of MDR-related genes (mdr1, mrp, DNA topoisomerase II alpha/beta) in non-small cell lung cancer (NSCLC).
Main Methods:
- Qualitative RT-PCR was used to assess mRNA expression of mdr1, mrp, and DNA topoisomerase II alpha/beta.
- p53 mutation status was previously determined in 51 NSCLC samples.
Main Results:
- p53 mutations were identified in 56% of NSCLC samples.
- Mdr1, mrp, topoisomerase alpha, and topoisomerase beta mRNA were expressed in 27%, 100%, 82%, and 94% of samples, respectively.
- No correlation was found between MDR gene expression and tumor type, stage, or lymph node status.
Conclusions:
- A significant association exists between p53 alterations and the expression of mdr1 (p=0.001) and DNA topoisomerase II alpha (p=0.003).
- These findings highlight the role of p53 in regulating MDR gene expression in NSCLC.