Endogenous retroviruses up-regulated in prostate cancer

Abstract

Human endogenous retroviruses of the HML-2 family show up-regulated expression in prostate tumors. This finding can be used in prostate cancer screening, diagnosis and therapy.

1 . An isolated polynucleotide comprising:
 (a) a nucleotide sequence of or corresponding to an RNA expression product of a human endogenous MMTV-like subgroup 2 (HML-2) retrovirus,   (b) a fragment of at least 7 nucleotides of (a),   (c) a nucleotide sequence having at least 75% identity to (a), or   (d) the complement of (a), (b), or (c),   wherein said HML-2 retrovirus is HERV-K(CH).   
     
     
         2 . The isolated polynucleotide of  claim 1 , wherein said RNA expression product comprises a Gag or Pol encoding sequence of HERV-K(CH). 
     
     
         3 . The isolated polynucleotide of  claim 2 , wherein said RNA expression product comprises a nucleotide sequence corresponding to a DNA sequence selected from the group consisting of SEQ ID NOS: 14-26. 
     
     
         4 . A method for the treatment or diagnosis of prostate cancer, testicular cancer, multiple sclerosis or insulin-dependent diabetes mellitus, the method comprising administering to a patient, or contacting a biological sample of the patient with, an isolated polynucleotide of  claim 1 . 
     
     
         5 . The method of  claim 4 , for the treatment of prostate cancer. 
     
     
         6 . An isolated polynucleotide having formula 5′-A-B-C-3′, wherein: -A- is a nucleotide sequence consisting of a nucleotides; -C- is a nucleotide sequence consisting of c nucleotides; and -B- is a nucleotide sequence consisting of either
 (a) a fragment of at least 7 nucleotides of or corresponding to an RNA expression product of a human endogenous MMTV-like subgroup 2 (HML-2) retrovirus, or 
 (b) the complement of a fragment (a), 
 wherein (i) said polynucleotide is neither (a) nor (b), (ii) a+c≧1, and (iii) said HML-2 retrovirus is HERV-K(CH). 
 
     
     
         7 . The isolated polynucleotide of  claim 6 , wherein said RNA expression product comprises a Gag or Pol encoding sequence of HERV-K(CH). 
     
     
         8 . The isolated polynucleotide of  claim 7 , wherein said RNA expression product comprises a nucleotide sequence corresponding to a DNA sequence selected from the group consisting of SEQ ID NOS: 14-26. 
     
     
         9 . The isolated polynucleotide of  claim 1  or  claim 6 , comprising a detectable label. 
     
     
         10 . A kit comprising primers for amplifying a template sequence contained within an isolated polynucleotide of  claim 1 , said kit comprising a first primer and a second primer, wherein said first primer is substantially complementary to said template sequence and said second primer is substantially complementary to a complement of said template sequence, wherein parts of said primers that have complementarity define the termini of said template sequence to be amplified. 
     
     
         11 . An isolated polypeptide comprising:
 (a) an amino acid sequence encoded by a nucleotide sequence of an RNA expression product of a human endogenous MMTV-like subgroup 2 (HML-2) retrovirus,   (b) a fragment of at least 7 amino acids of (a), or   (c) an amino acid sequence having at least 75% identity to (a),   wherein said HML-2 retrovirus is HERV-K(CH).   
     
     
         12 . The isolated polypeptide of  claim 11 , wherein (a) is an amino acid selected from the group consisting of SEQ ID NOS: 46-57. 
     
     
         13 . The isolated polypeptide of  claim 11 , wherein said RNA expression product comprises a Gag or Pol encoding sequence of HERV-K(CH). 
     
     
         14 . The isolated polypeptide of  claim 13 , wherein said RNA expression product comprises a nucleotide sequence corresponding to a DNA sequence selected from the group consisting of SEQ ID NOS: 14-26. 
     
     
         15 . An isolated polypeptide having a formula NH 2 -A-B-C-COOH, wherein -A- is an amino acid sequence consisting of a amino acids; -C- is an amino acid sequence consisting of c amino acids; and -B- is a fragment of at least 5 amino acids of an amino acid sequence encoded by a nucleotide sequence of an RNA expression product of a human endogenous MMTV-like subgroup 2 (HML-2) retrovirus, wherein (i) said polypeptide is not a fragment of an amino acid sequence encoded by a nucleotide sequence of said RNA expression product, (ii) a+c≧1, and (iii) wherein said HML-2 retrovirus is HERV-K(CH). 
     
     
         16 . The isolated polypeptide of  claim 15 , wherein -B- is a fragment of at least 5 amino acids of an amino acid sequence selected from the group consisting of SEQ ID NOS: 46-57. 
     
     
         17 . The isolated polypeptide of  claim 15 , wherein said RNA expression product comprises a Gag or Pol encoding sequence of HERV-K(CH). 
     
     
         18 . The isolated polypeptide of  claim 17 , wherein said RNA expression product comprises a nucleotide sequence corresponding to a DNA sequence selected from the group consisting of SEQ ID NOS: 14-26. 
     
     
         19 . A polypeptide of  claim 11  or  claim 15 , wherein said polypeptide is attached to a solid support. 
     
     
         20 . A polypeptide of  claim 11  or  claim 15 , wherein said polypeptide comprises a detectable label. 
     
     
         21 . An antibody for use in the diagnosis of prostate cancer, said antibody having binding affinity for the polypeptide of  claim 11  or  claim 15 . 
     
     
         22 . The antibody of  claim 21 , wherein said antibody is a monoclonal antibody. 
     
     
         23 . The antibody of  claim 21 , wherein said antibody is attached to a solid support. 
     
     
         24 . A pharmaceutical composition comprising:
 (a) a polynucleotide of  claim 1  or  claim 6 , a polypeptide of  claim 11  or  claim 17 , or an antibody of  claim 23 , and   (b) a pharmaceutically acceptable carrier.   
     
     
         25 . An immunogenic composition comprising:
 (a) a polynucleotide of  claim 1  or  claim 6  or a polypeptide of  claim 11  or  claim 17 , and   (b) a pharmaceutically acceptable carrier.   
     
     
         26 . The immunogenic composition of  claim 25 , further comprising an adjuvant. 
     
     
         27 . The immunogenic composition of  claim 25 , wherein said adjuvant comprises an oil-in-water emulsion or an aluminum salt. 
     
     
         28 . A method of raising an immune response in a patient, the method comprising administering an immunogenic dose of the immunogenic composition of  claim 25  to said patient. 
     
     
         29 . A composition comprising:
 (a) a prostate cell, and   (b) a polynucleotide of  claim 1  or  claim 6 , a polypeptide of  claim 11  or  claim 15 , or an antibody of  claim 21 , and   (c) a pharmaceutically acceptable carrier.