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

Taishi Harada, Jun Nagayama, Kimitoshi Kohno, Lyn A. Mickley, Tito Fojo, Michihiko Kuwano, Morimasa Wada

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Previous studies have shown that gene re-arrangements play a significant role in tumorigenesis. Gene re-arrangements involving the human multidrug resistant-I (MDR1) gene have been identified as a mechanism for MDR1 overexpression in human malignant cells. In 2 multidrug-resistant human cancer sublines with high levels of MDR1 and P-glycoprotein (MCF7/TX400 and S48-3s/Adr 10), 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 λ 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 χ-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. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)506-511
Number of pages6
JournalInternational Journal of Cancer
Volume86
Issue number4
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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