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Alu‐associated interstitial deletions and chromosomal re‐arrangement in 2 human multidrug‐resistant cell lines
Author(s) -
Harada Taishi,
Nagayama Jun,
Kohno Kimitoshi,
Mickley Lyn A.,
Fojo Tito,
Kuwano Michihiko,
Wada Morimasa
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000515)86:4<506::aid-ijc10>3.0.co;2-8
Subject(s) - alu element , biology , gene , homologous recombination , genetics , microbiology and biotechnology , human genome , genome
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 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. Int. J. Cancer 86:506–511, 2000. © 2000 Wiley‐Liss, Inc.