Renal nuclear matrix proteins, polynucleotide sequences encoding them, and their use

Abstract

Nuclear matrix proteins (NMP) are useful markers in diagnosing and monitoring the stage of malignancy of a cell, and in treating cell proliferative disorders associated with the NMP.

What is claimed is:  
     
         1 . A purified nuclear matrix protein that is present in normal renal cells but absent in cancerous renal cells, or that is absent in normal renal cells but present in cancerous renal cells.  
     
     
         2 . The protein or fragment as claimed in    claim 1   , wherein the protein is RCNL-1.  
     
     
         3 . The protein or fragment of    claim 1   , wherein the protein is selected from the group consisting of RCCA-1, RCCA-2, RCCA-3, RCCA-4, and RCCA-5.  
     
     
         4 . A purified polynucleotide sequence encoding a protein or fragment of    claim 1   .  
     
     
         5 . A purified polynucleotide sequence which hybridizes to the polynucleotide sequence of    claim 4   .  
     
     
         6 . A host cell transformed with the polynucleotide of    claim 4   .  
     
     
         7 . A recombinant expression vector containing the polynucleotide of    claim 4   .  
     
     
         8 . The vector of    claim 7   , wherein the vector is a virus.  
     
     
         9 . The vector of    claim 8   , wherein the virus is an RNA virus.  
     
     
         10 . The vector of    claim 9   , wherein the RNA virus is a retrovirus.  
     
     
         11 . The vector of    claim 7   , wherein the vector is a liposome.  
     
     
         12 . The vector of    claim 11   , wherein the liposome is target-specific.  
     
     
         13 . The vector of    claim 12   , wherein the liposome is targeted with an antibody.  
     
     
         14 . The vector of    claim 7   , wherein the vector is a plasmid.  
     
     
         15 . An antibody which binds to the protein of    claim 1   .  
     
     
         16 . A method for detecting a cell proliferative disorder in a subject, comprising contacting a cellular component from the subject with a reagent which binds to a cellular component associated with a cell proliferative disorder.  
     
     
         17 . The method of    claim 16   , wherein the cellular component is taken from the subject's kidney.  
     
     
         18 . The method of    claim 17   , wherein the cellular component is nucleic acid.  
     
     
         19 . The method of    claim 18   , wherein the nucleic acid is DNA.  
     
     
         20 . The method of    claim 18   , wherein the nucleic acid is RNA.  
     
     
         21 . The method of    claim 17   , wherein the cellular component is protein.  
     
     
         22 . The method of    claim 16   , wherein the reagent is a probe.  
     
     
         23 . The method of    claim 22   , wherein the probe is nucleic acid.  
     
     
         24 . The method of    claim 22   , wherein the probe is an antibody.  
     
     
         25 . The method of    claim 24   , wherein the antibody is polyclonal.  
     
     
         26 . The method of    claim 24   , wherein the antibody is monoclonal.  
     
     
         27 . The method of    claim 22   , wherein the probe is detectably labeled.  
     
     
         28 . The method of    claim 27   , wherein the label is selected from the group consisting of a radioisotope, a bioluminescent compound, a chemiluminescent compound, a fluorescent compound, a metal chelate, and an enzyme.  
     
     
         29 . A method of treating a cell proliferative disorder associated with a protein selected from the group consisting of RCCA-1, RCCA-2, RCCA-3, RCCA-4, RCCA-5, and RCNL-1, comprising administering to a subject with the disorder a therapeutically effective amount of reagent which blocks or enhances the function of the protein.  
     
     
         30 . The method of    claim 29   , wherein the reagent is an antisense polynucleotide sequence.  
     
     
         31 . The method of    claim 29   , wherein the reagent is a polynucleotide sequence encoding a protein selected from the group consisting of RCCA-1, RCCA-2, RCCA-3, RCCA-4, RCCA-5, and RCNL-1.  
     
     
         32 . The method of    claim 29   , wherein the reagent is an antibody.  
     
     
         33 . The method of    claim 32   , wherein the antibody is monoclonal.  
     
     
         34 . The method of    claim 29   , wherein the cell proliferative disorder is in renal tissue.  
     
     
         35 . A method of gene therapy, comprising introducing into the cells of a host subject an expression vector comprising a nucleotide sequence encoding a protein of    claim 1   .  
     
     
         36 . The method of    claim 35   , wherein the expression vector is introduced into the cells of the host subject ex vivo, yielding transformed cells, and the transformed cells then are reintroduced into the subject.  
     
     
         37 . The method of    claim 36   , wherein the expression vector is an RNA virus.  
     
     
         38 . The method of    claim 37   , wherein the RNA virus is a retrovirus.  
     
     
         39 . The method of    claim 36   , wherein the subject is human.  
     
     
         40 . A method for identifying a composition which blocks or enhances the function of an NMP of renal cells, which method comprises: 
 (a) incubating NMP-containing renal cells with a test composition under conditions that allow the renal cells and test composition to interact, and then    (b) measuring whether the test composition causes blocking or enhancement of the function of an NMP of the renal cells.    
     
     
         41 . The method of    claim 40   , wherein the NMP is selected from the group consisting of RCCA-1, RCCA-2, RCCA-3, RCCA-4, RCCA-5, and RCNL-1.  
     
     
         42 . The method of    claim 40   , wherein the effect being measured is blocking of the function of the NMP.  
     
     
         43 . The method of    claim 40   , wherein the effect being measured is enhancement of the function of the NMP.  
     
     
         44 . A kit useful for the detection of a cell-proliferative disorder associated with a protein of    claim 1   , said kit comprising a probe for identifying a protein or fragment of    claim 1    or a polynucleotide sequence encoding a protein or fragment of    claim 1   .  
     
     
         45 . The kit of    claim 44   , wherein the probe is an antibody capable of binding to the protein or fragment.  
     
     
         46 . The kit of    claim 44   , wherein the probe is a polynucleotide probe capable of hybridizing with the polynucleotide sequence encoding the protein or fragment.  
     
     
         47 . The kit of    claim 46   , further comprising a container containing an oligonucleotide primer for amplification of the polynucleotide sequence encoding the protein or fragment.