Human polyhomeotic 2 (hph2) acts as an oncogene

Abstract

A human oncogene and its expression products can be used as diagnostic, prognostic, and therapeutic tools for neoplastic disorders. Nucleotide sequences of the gene can also be used to identify a p34.3 region of a human chromosome 1.

1 . An isolated and purified human polyhomeotic 2 protein having the amino acid sequence shown in SEQ ID NO:2.  
     
     
         2 . An isolated and purified human polyhomeotic 2 protein having an amino acid sequence which is at least 85% identical to the amino acid sequence shown in SEQ ID NO:2.  
     
     
         3 . An isolated and purified human polyhomeotic 2 polypeptide consisting of at least 14 contiguous amino acids selected from the amino acid sequence shown in SEQ ID NO:2.  
     
     
         4 . A human polyhomeotic 2 fusion protein comprising a first protein segment and a second protein segment fused together by means of a peptide bond, wherein the first protein segment consists of at least 14 contiguous amino acids of a human polyhomeotic 2 protein.  
     
     
         5 . A preparation of antibodies which specifically bind to a human polyhomeotic 2 protein.  
     
     
         6 . An isolated and purified subgenomic polynucleotide consisting of at least 11 contiguous nucleotides selected from the nucleotide sequence shown in SEQ ID NO:1.  
     
     
         7 . An expression construct for expressing all or a portion of a human polyhomeotic 2 protein comprising: 
 a promoter; and    a polynucleotide segment encoding at least 14 contiguous amino acids of a human polyhomeotic 2 protein, wherein the polynucleotide segment is located downstream from the promoter, wherein transcription of the polynucleotide segment initiates at the promoter.    
     
     
         8 . A homologously recombinant cell having incorporated therein a new transcription initiation unit, wherein the new transcription inititation unit comprises: 
 (a) an exogenous regulatory sequence;    (b) an exogenous exon; and    (c) a splice donor site, wherein the transcription initiation unit is located upstream of a coding sequence of an hph2 gene, wherein the exogenous regulatory sequence directs transcription of the coding sequence of the hph2 gene.    
     
     
         9 . A method of identifying neoplastic tissue of a human, comprising: 
 comparing the expression of a polyhomeotic 2 gene in a first tissue of a human suspected of being neoplastic with the expression of a polyhomeotic 2 gene in a second tissue of the human which is normal, wherein overexpression of the human polyhomeotic 2 gene in the first tissue identifies the first tissue as being neoplastic.    
     
     
         10 . A method to aid in the diagnosis or prognosis of neoplasia in a human, comprising: 
 comparing a polyhomeotic 2 gene, mRNA, or protein in a first tissue of a human suspected of being neoplastic with a polyhomeotic 2 gene, mRNA, or protein in a second tissue of a human which is normal, wherein a difference between the polyhomeotic 2 genes, mRNAs, or proteins in the first and second tissues indicates neoplasia in the first tissue.    
     
     
         11 . A method to aid in detecting a genetic predisposition to neoplasia in a human, comprising: 
 comparing a polyhomeotic 2 gene, mRNA, or protein in a fetal. tissue of a human with a wild-type human polyhomeotic 2 gene, mRNA, or protein, wherein a difference between the polyhomeotic 2 gene, mRNA, or protein in the fetal tissue of the human and the wild-type human polyhomeotic 2 gene, mRNA, or protein indicates a genetic predisposition to neoplasia in the human.    
     
     
         12 . A method of identifying a human chromosome 1, comprising the steps of: 
 contacting a preparation of metaphase human chromosomes with a nucleotide probe comprising at least 12 contiguous nucleotides selected from the nucleotide sequence shown in SEQ ID NO:1; and    detecting a chromosome which specifically hybridizes to the nucleotide probe, wherein a chromosome which specifically hybridizes to the nucleotide probe is identified as a human chromosome 1.    
     
     
         13 . A therapeutic composition for treating neoplasia, comprising: 
 a therapeutically effective amount of an antisense hph2 polynucleotide; and    a pharmaceutically acceptable carrier.    
     
     
         14 . A therapeutic composition comprising: 
 a therapeutically effective amount of an antibody which specifically binds to a human polyhomeotic 2 protein; and    a pharmaceutically acceptable carrier.    
     
     
         15 . A method of treating neoplasia, comprising the step of administering to a patient with neoplasia a therapeutically effective amount of a therapeutic hph2 composition, whereby the patient's neoplasia is reduced.  
     
     
         16 . A method of inducing a cell to change its pattern of differentiation, comprising the step of contacting a cell with an effective amount of a composition comprising all or a portion of a human polyhomeotic 2 gene or expression product, wherein said all or a portion of the human polyhomeotic 2 gene or expression product is capable of inducing the cell to change its pattern of differentiation.