Abstract
Overexpression of the multidrug resistanceMDR1 gene is thought to contribute to drug resistance in non-responsive cancers like colorectal carcinoma. Little is known about the mechanisms by which expression ofMDR1 is regulated in human tumours. However, there is growing evidence that regulation primarily takes place at the transcriptional level and that the process of tumour progression is related to activation of theMDR1 gene. Mutations in thep53 tumour-suppression gene occur in approximately 70% of colorectal cancers. As a transcriptional regulator,p53 might be involved in regulation ofMDR1 expression in these tumours. We therefore determinedMDR1 expression using the differential polymerase chain reaction technique in 30 colorectal tumours (4 primaries and 26 metastates) and correlated our results with previously reported data onp53 in the same group of patients. We found a significant positive correlation betweenp53 andMDR1 expression inp53-mutated tumours (P=0.005;r=0.596), but not in tumours without ap53 mutation. In addition, we observed a tendency towards higherMDR1 expression levels in tumours carryingp53 mutations (P=0.14) compound to wild-typep53 tumours. These data indicate that mutantp53 may play a role in the regulation ofMDR1 expression in human cholorectal cancer.
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de Kant, E., Heide, I., Thiede, C. et al. MDR1 expression correlates with mutantp53 expression in colorectal cancer metastases. J Cancer Res Clin Oncol 122, 671–675 (1996). https://doi.org/10.1007/BF01209030
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DOI: https://doi.org/10.1007/BF01209030