Therapeutic and diagnostic applications of prostatic acid phosphatase in prostate cancer

Abstract

Presented is a therapeutic method to treat prostate carcinomas in mammals comprising the administration of cellular PAcP protein. Also presented is a method to diagnose androgen-insensitive prostate carcinomas by determining the expression level of cellular PAcP in the prostate carcinomas, a decrease in expression being indicative of androgen-insensitivity. A promoter region that is specifically expressed in prostate tissue is presented, as is a xenograft animal model that mimics human prostate carcinomas in the expression of cellular PAcP.

1 . A therapeutic method for treating a mammalian prostate carcinoma, comprising the step of administering a therapeutically effective amount of cellular PAcP protein to the carcinoma.  
   
   
       2 . The therapeutic method of  claim 1 , wherein the cellular PAcP protein is from a human.  
   
   
       3 . The therapeutic method of  claim 1 , wherein the cellular PAcP protein is in a liposome.  
   
   
       4 . The therapeutic method of  claim 3 , wherein the liposome is comprised of lipofectin.  
   
   
       5 . The therapeutic method of  claim 1 , wherein the cellular PAcP is coupled to a monoclonal antibody.  
   
   
       6 . The therapeutic method of  claim 5 , wherein the monoclonal antibody is immunologically specific to a human prostate cancer cell.  
   
   
       7 . The therapeutic method of  claim 1 , wherein the step of administering the cellular PAcP protein is comprised of the steps of 
 A) administering a nucleic acid comprised of the coding sequence of cellular PAcP to the prostate carcinoma; and    B) allowing the cellular PAcP coding sequence to be expressed in the prostate carcinoma.    
   
   
       8 . The therapeutic method of  claim 7 , wherein the nucleic acids administered are comprised of a pCMV-neo expression vector operably linked to the coding sequence of cellular PAcP protein.  
   
   
       9 . The therapeutic method of  claim 7 , wherein the coding sequence of cellular PAcP protein encodes Genbank Accession No. M34840.  
   
   
       10 . The therapeutic method of  claim 7 , wherein the coding sequence of cellular PAcP is Genbank Accession No. M34840.  
   
   
       11 . The therapeutic method of  claim 7 , wherein the nucleic acid administered comprises the coding sequence of cellular PAcP operably linked to a viral vector selected from the group consisting of herpes simplex virus, cytomegalovirus, murine leukemia virus, recombinant adeno-associated virus, a recombinant adenoviral vector, human immunodeficiency virus and feline immunodeficiency virus.  
   
   
       12 . The therapeutic method of  claim 7 , wherein the administered nucleic acid comprises the coding sequence of cellular PAcP operably linked to a promoter selected from the group consisting of the cytomeglovirus promoter and the PAcP promoter.  
   
   
       13 . A kit to carry out the therapeutic method of  claim 1 , comprising instructions for the therapeutic method of  claim 1  and a container containing a reagent selected from the group consisting of purified cellular PAcP protein and a nucleic acid encoding cellular PAcP.  
   
   
       14 . A method to diagnose androgen-insensitive prostate carcinomas comprising the step of determining the expression of cellular PAcP protein in the prostate carcinoma, a decrease in the expression being indicative of the androgen-insensitive nature of the carcinoma.  
   
   
       15 . The diagnostic method of  claim 14 , in which the step of determining the expression is comprised of the step of quantifying the concentration of cellular PAcP protein in the prostate carcinoma.  
   
   
       16 . The diagnostic method of  claim 15 , where in cellular PAcP protein is quantified by an antibody immunologically specific to the cellular PAcP protein.  
   
   
       17 . The diagnostic method of  claim 14 , in which the step of determining the expression is comprised of the step of quantifying the activity of cellular PAcP in the prostate carcinoma.  
   
   
       18 . The diagnostic method of  claim 17 , wherein the activity of cellular PAcP is quantified by measuring acid phosphatase activity.  
   
   
       19 . The diagnostic method of  claim 14 , in which the step of determining the expression is comprised of the step of quantifying the concentration of cellular PAcP mRNA in the prostate carcinoma.  
   
   
       20 . The diagnostic method of  claim 19 , wherein the cellular PAcP mRNA is quantified by a method selected from the group consisting of PCR, Northern and Southern.  
   
   
       21 . The diagnostic method of  claim 19 , wherein the cellular PAcP mRNA is quantified by its specific hybridization to a nucleic acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4 and at least 15 consecutive nucleotides of M34840.  
   
   
       22 . A kit to diagnose androgen-insensitive prostate carcinomas, comprising instructions to carry the diagnostic method of  claim 14  and a container containing a reagent selected from the group consisting of an antibody immunologically specific to cellular PAcP protein, at least one a nucleic acid that hybridizes at moderate stringency to Genbank Accession No. M34840 and a reagent to assay acid phosphatase activity.  
   
   
       23 . A promoter region useful for prostate specific expression, comprising the regulatory regions of a PAcP gene.  
   
   
       24 . The promoter of  claim 23 , which is the regulatory regions of a human PAcP gene.  
   
   
       25 . The promoter of  claim 24 , which is comprised of at least 100 consecutive nucleic acids of a nucleic acid sequence selected from the group consisting of Genbank Accession No. U07083 and Genbank Accession No. X74961.  
   
   
       26 . The promoter of  claim 25 , which is the −1356 to +87 nucleotide region, where nucleotide 1 is the transcription start site, of a nucleic acid sequence selected from the group consisting of Genbank Accession No. U07083 and Genbank Accession No. X74961.  
   
   
       27 . A xenograft animal model for studying human prostate cancers, comprising an athymic mammal hosting at least one transgenic human prostate carcinoma cell.  
   
   
       28 . The xenograft animal model of  claim 26 , wherein the mammal is a mouse.  
   
   
       29 . The xenograft animal model of  claim 26 , wherein the transgenic human prostate carcinoma cell is derived from a cell line selected from the group consisting of LNCaP, PC-3 and DU145.  
   
   
       30 . The xenograft animal model of  claim 26 , wherein the transgenic human prostate carcinoma cell comprises an exogenous nucleic acid sequence encoding cellular PAcP protein.  
   
   
       31 . The xenograft animal model of  claim 29 , wherein the exogenous nucleic acid sequence encodes human cellular PAcP protein.  
   
   
       32 . The xenograft animal model of  claim 29 , wherein the exogenous nucleic acid expresses human cellular PAcP protein.