Abstract
The lung resistance-related protein (LRP) was identified as the human major vault protein (MVP), and is overexpressed in various multidrug-resistant cancer cell lines and clinical samples. We characterized DNA sequences upstream to the transcription initiation site of the MVP gene in the human non-small cell lung cancer cell line SW-1573. A 1.9-kb and a shortened 0.7-kb fragment of the 5'-upstream genomic region show strong promoter activity in chloramphenicol acetyltransferase (CAT) reporter assays. The promoter is TATA-less and contains an inverted CCAAT-box and a Sp1 site located near to a p53 binding motif. An alternative 3'-splice site of intron 1 results in a splicing variant within the 5'-untranslated region of MVP mRNA.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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5' Untranslated Regions
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Alternative Splicing
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Base Sequence
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / metabolism
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Chloramphenicol O-Acetyltransferase / metabolism
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Cloning, Molecular
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism
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Doxorubicin / pharmacology
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Drug Resistance, Multiple / genetics*
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Electrophoresis, Agar Gel
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Enzyme-Linked Immunosorbent Assay
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Genes, Reporter
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Humans
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Introns
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism
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Models, Genetic
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Molecular Sequence Data
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Plasmids / metabolism
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Promoter Regions, Genetic*
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RNA, Messenger
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Analysis, DNA
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Sp1 Transcription Factor / genetics
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TATA Box
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Transcription, Genetic
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism
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Up-Regulation
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Vault Ribonucleoprotein Particles / genetics
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Vault Ribonucleoprotein Particles / metabolism
Substances
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5' Untranslated Regions
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Neoplasm Proteins
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RNA, Messenger
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Sp1 Transcription Factor
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Tumor Suppressor Protein p53
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Vault Ribonucleoprotein Particles
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major vault protein
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Doxorubicin
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Chloramphenicol O-Acetyltransferase
Associated data
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GENBANK/AJ238509
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GENBANK/AJ238510
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GENBANK/AJ238511
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GENBANK/AJ238512
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GENBANK/AJ238513
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GENBANK/AJ238514
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GENBANK/AJ238515
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GENBANK/AJ238516
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GENBANK/AJ238517
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GENBANK/AJ238518
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GENBANK/AJ238519