Multidrug resistance protein
AssigneeQueen's University at Kingston
InventorsRoger G. Deeley, Susan P. C. Cole
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Abstract
A novel protein associated with multidrug resistance in living cells and capable of conferring multidrug resistance on a cell is disclosed and nucleic acids encoding the novel isoforms are disclosed. Transformant cell lines which express the nucleic acid encoding the novel protein are also disclosed. Further, diagnostic and treatment methods using the novel protein, nucleic acids and cell lines are also disclosed.
Claims33
An isolated nucleic acid comprising a nucleotide sequence encoding a protein having the biological activity of multidrug resistance-associated protein, MRP, and having at least 70% homology to the amino acid sequence shown in SEQ ID NO:
- 2 including resistance to doxorubicin, on a drug sensitive mammalian cell when the protein is expressed in the cell, said multidrug resistance not being substantially reversed by chemosensitizers which reverse P-glycoprotein-mediated multidrug resistance.
An isolated nucleic acid encoding a protein comprising the amino acid sequence shown in SEQ ID NO:
- 2.
An isolated naturally-occurring nucleic acid which hybridizes under stringent conditions to a nucleic acid which encodes a protein comprising the amino acid sequence shown in SEQ ID NO:
- 2 and encodes a protein having the biological activity of multidrug resistance-associated protein, MRP, which has at least 60% homology to the amino acid sequence shown in SEQ ID NO:
- 2.
An isolated nucleic acid which confers multidrug resistance on a cell comprising the nucleotide sequence shown in SEQ ID NO:
- 1.
An isolated nucleic acid which confers multidrug resistance on a cell comprising a nucleotide sequence encoding a protein comprising an amino acid sequence represented by the formula V-W-X-Y-Z, wherein V are amino acid residues corresponding to amino acid residues from about 1 to 660 of SEQ ID NO:
- 2, W are amino acid residues of a nucleotide binding fold substantially homologous with amino acid residues from about 661 to 810 of SEQ ID NO:
- 2, X are amino acid residues corresponding to amino acid residues from about 811 to 1309 of SEQ ID NO:
- 2, Y are amino acid residues of a nucleotide binding fold substantially homologous with amino acid residues from about 1310 to 1469 of SEQ ID NO:
- 2 and Z are amino acid residues corresponding to amino acid residues from about 1470 to 1531 of SEQ ID NO:
- 2.
An isolated nucleic acid which is antisense to a nucleic acid comprising a nucleotide sequence shown in SEQ ID NO:
- 1.
A recombinant expression vector suitable for transformation of a host cell comprising a DNA molecule having a nucleotide sequence shown in SEQ ID NO:
- 1 and a regulatory sequence operatively linked to the DNA molecule.
A diagnostic kit for identifying multidrug resistant tumor cells comprising a nucleotide probe complementary to the sequence, or an oligonucleotide fragment thereof, shown in SEQ ID NO:
- 1 for hybridization with mRNA from a sample of tumor cells;
- means for detecting the nucleotide probe bound to mRNA;
- means determining the amount of mRNA in the sample;
- and means for comparing the amount of mRNA in the sample with a standard.
A recombinant expression vector suitable for transformation of a host cell comprising a DNA molecule having a nucleotide sequences encoding a protein having the amino acid sequence shown in SEQ ID NO:
- 2 and a regulatory sequence operatively linked to the DNA molecule.
Dependencies are inferred from the claim text.