Nuclear matrix proteins, polynucleotide sequences encoding them, and their use

Abstract

A novel prostate cancer marker is described that is found in cancerous and normal cells of the prostate in individuals that have prostate cancer but is not found in the prostate of individuals without the disease. In addition, it is present in normal tissue adjacent to the tumor tissue in individuals having prostate cancer. It is, however, absent in the prostate of individuals without the disease. Methods employing the novel prostate cancer marker of the invention to predict the occurrence of the prostate disease, monitor the progression of prostate cancer and effect the treatment of prostate cancer, are also described.

What is claimed is:  
     
         1 . A purified protein which is found in cancerous and normal cells of a prostate in individuals that have prostate cancer but is not found in prostate cells of individuals without prostate cancer, wherein an individual is defined as having prostate cancer if a pathologically identified lesion is present within the prostate, or an antigenic fragment thereof.  
     
     
         2 . The protein of  claim 1 , wherein said protein is expressed in the cytoplasm and membrane and is not expressed inside the nucleus.  
     
     
         3 . The protein of  claim 1 , wherein said protein is expressed at a higher level in prostate cells of individuals with aggressive prostate cancer than in individuals with non-aggressive prostate lesions.  
     
     
         4 . The protein of  claim 1 , wherein said protein is expressed in intra-prostatic tissues, lymph nodes, and seminal vesicles of individuals having metastatic prostate cancer.  
     
     
         5 . The protein of  claim 1 , wherein said protein is expressed at higher levels outside the nucleus.  
     
     
         6 . The protein of  claim 1 , wherein said protein has a molecular weight of about 40 kD and a pl of about 6.73.  
     
     
         7 . The protein fragment of  claim 1 , wherein said protein fragment comprises a peptide sequence selected from the group consisting of VSNTPLPGVFTK, TIGDNQK, DAYPGQIS, and DSGQGY.  
     
     
         8 . The protein of  claim 1 , wherein said protein is expressed in individuals with prostate cancer and in individuals with the disease even in biopsy samples that are morphologically negative.  
     
     
         9 . The protein of  claim 1 , wherein said protein is detectable in a biological sample more than two years prior to detection of cancer based on the Gleason score.  
     
     
         10 . The protein of  claim 1 , wherein said protein is derived from a human.  
     
     
         11 . A method for determining whether an individual will develop or already has prostate cancer from a biological sample comprising determining the presence or absence of the protein or antigenic fragment of  claim 1  in the biological sample, wherein the presence of said protein or antigenic fragment indicates that the individual will develop or already has prostate cancer.  
     
     
         12 . The method of  claim 11 , wherein said sample is obtained from tissue or a biological fluid.  
     
     
         13 . The method of  claim 12 , wherein said tissue is a biopsy tissue.  
     
     
         14 . The method of  claim 12 , wherein said biological fluid is selected from the group consisting of blood, serum, fecal matter, urine, semen, seminal fluid and plasma.  
     
     
         15 . The method of  claim 11 , wherein said method is further used to monitor the progression of prostate cancer.  
     
     
         16 . The method of  claim 11 , wherein said method further comprises determining the expression level of prostate specific antigen in said prostate cancer cells and correlating said expression level to that of said protein of  claim 1 .  
     
     
         17 . The method of  claim 16 , wherein the expression levels of said prostate specific antigen and said protein of  claim 1  are determined from a serum sample.  
     
     
         18 . The method of  claim 16 , wherein the expression level of said prostate specific antigen is determined from a serum sample and the expression level of said protein of  claim 1  is determined from a tissue sample.  
     
     
         19 . The method of  claim 16 , wherein said sample is a tissue or a biological fluid sample.  
     
     
         20 . The method of  claim 19 , wherein said tissue is a biopsy tissue.  
     
     
         21 . The method of  claim 19 , wherein said biological fluid sample is selected from the group consisting of blood, serum, fecal matter, urine, semen, seminal fluid and plasma.  
     
     
         22 . The method of  claim 13 , wherein said method further comprises determining the Gleason scores of an individual who is the source of said sample and correlating said Gleason scores with expression level of said protein of  claim 1 .  
     
     
         23 . A purified polynucleotide sequence encoding the protein of  claim 1  or said antigenic fragment thereof.  
     
     
         24 . A purified polynucleotide sequence which hybridizes to said polynucleotide of  claim 23 .  
     
     
         25 . A host cell transformed with said polynucleotide sequence of  claim 23 .  
     
     
         26 . A host cell transformed with said polynucleotide sequence of  claim 24 .  
     
     
         27 . A recombinant expression vector containing said polynucleotide sequence of claims  23 .  
     
     
         28 . A recombinant expression vector containing said polynucleotide sequence of claims  24 .  
     
     
         29 . The recombinant expression vector of claims  27  or  29 , wherein said vector is a virus.  
     
     
         30 . The recombinant expression vector of  claim 29 , wherein said virus is a RNA virus.  
     
     
         31 . The recombinant expression vector of  claim 30 , wherein said RNA virus is a retrovirus.  
     
     
         32 . The recombinant expression vector of claims  27  or  29 , wherein said vector is a liposome.  
     
     
         33 . The recombinant expression vector of  claim 32 , wherein said liposome is a target-specific liposome which may be targeted with an antibody or ligand.  
     
     
         34 . The recombinant expression vector of  claim 27  or  29 , wherein said vector is plasmid.  
     
     
         35 . A method for determining whether an individual will develop or already has prostate cancer from a sample containing nucleic acids, comprising 
 (a) hybridizing a complement of a polynucleotide sequence encoding the protein of  claim 1  or an antigenic fragment thereof, to at least one of the nucleic acids of said sample, thereby forming a hybridization complex; and    (b) detecting said hybridization complex, wherein the presence of said hybridization complex correlates with the presence of said sequence encoding the protein of  claim 1  or said immunogenic fragment thereof in said sample and indicates that the individual will develop or already has prostate cancer.    
     
     
         36 . The method of  claim 35 , wherein said nucleic acids of said sample are amplified by polymerase chain reaction prior to the hybridizing step.  
     
     
         37 . The method of claims  35  or  36 , wherein said sample is a tissue or a biological fluid sample.  
     
     
         38 . The method of  claim 37 , wherein said tissue is a biopsy tissue.  
     
     
         39 . The method of  claim 37 , wherein said biological fluid sample is selected from the group consisting of blood, serum, fecal matter, urine, semen, seminal fluid and plasma.  
     
     
         40 . The method of  claim 35  or  36 , wherein said method is further used to predict the occurrence of the prostate cancer and monitor the progression of prostate cancer.  
     
     
         41 . An isolated or purified antibody which binds to said protein of  claim 1  or said antigenic fragment thereof.  
     
     
         42 . The isolated or purified antibody of  claim 41 , wherein said antibody is polyclonal or monoclonal.  
     
     
         43 . A method of producing an antibody of  claim 41 , wherein said antibody is capable of differentiating between cancerous prostate and normal prostate tissues, said method comprising 
 (a) selecting the protein or antigenic fragment of  claim 1  as an antigen,    (b) raising an antibody against said antigen, and    (c) recovering said antibody.