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

Abstract

Nuclear matrix proteins (NMP) which are characterized by a defined expression in tissue, particularly prostate tissue, are provided. These NMPs are useful markers in diagnosing and monitoring the stage of malignancy of a cell and treating cell proliferative disorders associated with the NMP. Also provided are substantially purified polypeptides and nucleotide sequences encoding the NMPs of the invention.

1 . A method of determining the presence or absence of a metastatic cell, comprising determining the presence or absence of a nuclear matrix protein that is present in a metastatic cell but absent in a non-metastatic cell.  
     
     
         2 . The method as claimed in  claim 1 , wherein said determination step is performed on a sample of prostate cells.  
     
     
         3 . The method as claimed in  claim 2 , wherein the nuclear matrix protein is AM-I having a molecular weight of about 40 kD and a pI of about 6.73, which is present in a metastatic prostate cell but absent in a non-metastatic prostate cell.  
     
     
         4 . The method as claimed in  claim 3 , wherein said determination step is performed with an antibody directed against AM-1 or an immunogenic fragment thereof.  
     
     
         5 . A purified nuclear matrix protein which is present in cancerous prostate cells but absent in normal prostate cells selected from the group consisting of: 
 (a) D-1 having a molecular weight of about 63 kD and a pI of about 8.55,    (b) D-2 having a molecular weight of about 40 kD and a pI of about 5.91, and    (c) D-3 having a molecular weight of about 33 kD and a pI of about 6.97; or an immunogenic fragment of one of said proteins (a)-(c).    
     
     
         6 . The protein of  claim 5 , wherein the protein is D-1 having a molecular weight of about 63 kD and a pI of about 8.55.  
     
     
         7 . The protein of  claim 6 , which includes at least one sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3.  
     
     
         8 . The protein of  claim 5 , wherein the protein is D-2 having a molecular weight of about 40 kD and a pI of about 5.91.  
     
     
         9 . The protein of  claim 8 , which includes at least one sequence selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 5.  
     
     
         10 . The protein of  claim 5 , wherein the protein is D-3 having a molecular weight of about 33 kD and a pI of about 6.97.  
     
     
         11 . The protein of  claim 10 , which includes SEQ ID NO: 6.  
     
     
         12 - 41 . (canceled)