MDR1 expression correlates with mutant p53 expression in colorectal cancer metastases.
Overexpression of the multidrug resistance MDR1 gene is thought to contribute to drug resistance in non-responsive cancers like colorectal carcinoma. Little is known about the mechanisms by which expression of MDR1 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 the MDR1 gene. Mutations in the p53 tumour-suppression gene occur in approximately 70% of colorectal cancers. As a transcriptional regulator, p53 might be involved in regulation of MDR1 expression in these tumours. We therefore determined MDR1 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 on p53 in the same group of patients. We found a significant positive correlation between p53 and MDR1 expression in p53-mutated tumours (P = 0.005; r = 0.596), but not in tumours without a p53 mutation. In addition, we observed a tendency towards higher MDR1 expression levels in tumours carrying p53 mutations (P = 0.14) compound to wild-type p53 tumours. These data indicate that mutant p53 may play a role in the regulation of MDR1 expression in human cholorectal cancer.
Academic Hospital Utrecht, Dept. Internal Medicine-G02228, The Netherlands.
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de Kant
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Heide
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Thiede
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Herrmann
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Rochlitz
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D009362:Neoplasm Metastasis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016159:Tumor Suppressor Protein p53