Alu-associated interstitial deletions and chromosomal re-arrangement in 2 human multidrug-resistant cell lines.

Abstract

Previous studies have shown that gene re-arrangements play a significant role in tumorigenesis. Gene re-arrangements involving the human multidrug resistance-1 (MDR1) gene have been identified as a mechanism for MDR1 over-expression in human malignant cells. In 2 multidrug-resistant human cancer sublines with high levels of MDR1 and P-glycoprotein (MCF7/TX400 and S48-3s/Adr10), hybrid mRNAs containing sequences from MDR1 and an unrelated gene have previously been identified. To characterize and determine the site of the re-arrangements resulting in generation of hybrid mRNAs, we first constructed a lambda phage library extending over a contiguous genomic region of 100 kb and containing the region upstream of MDR1. In MCF7/TX400 cells, homologous recombination was observed involving an Alu repeat 80 kb upstream of the MDR1 gene, with a 79 bp intra-Alu deletion flanked by chi-like sequences at the re-arrangement junction. By contrast, non-homologous recombination was observed in S48-3s/Adr10 cells with Alu repeats near the junction sequence. While the specific features of the breakpoints appear to be different, Alu repeats might be involved in both gene re-arrangements. The gene re-arrangements at or near the Alu sequence should be regarded as potentially involved in the transcriptional activation of human MDR1.

• Authors: T Harada, J Nagayama, K Kohno, L A Mickley, T Fojo, M Kuwano, M Wada
• Journal: International journal of cancer (Int J Cancer) Vol. 86 Issue 4 Pg. 506-11 (May 15 2000) ISSN: 0020-7136 [Print] United States
• PMID: 10797263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Alu Elements
• Base Sequence
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Gene Deletion
• Gene Rearrangement
• Humans
• Molecular Sequence Data
• Promoter Regions, Genetic
• Tumor Cells, Cultured