MN Gene and Protein

Abstract

A new gene—MN—and proteins/polypeptides encoded therefrom are disclosed. Recombinant nucleic acid molecules for expressing MN proteins/polypeptides and recombinant proteins are provided. Expression of the MN gene is disclosed as being associated with tumorigenicity, and the invention concerns methods and compositions for detecting and/or quantitating MN antigen and/or MN-specific antibodies in vertebrate samples that are diagnostic/prognostic for neoplastic and pre-neoplastic disease. Test kits embodying the immunoassays of this invention are provided. MN-specific antibodies are disclosed that can be used diagnostically/prognostically, therapeutically, for imaging, and/or for affinity purification of MN proteins/polypeptides. Also provided are nucleic acid probes for the MN gene as well as test kits comprising said probes. The invention also concerns vaccines comprising MN proteins/polypeptides which are effective to immunize a vertebrate against neoplastic diseases associated with the expression of MN proteins. The invention still further concerns antisense nucleic acid sequences that can be used to inhibit MN gene expression.

1 . An isolated nucleic acid containing at least fifty nucleotides wherein the nucleotide sequence for said nucleic acid is selected from the group consisting of:
 (a) SEQ. ID. NOS.: 1, 5, 23 and nucleotide sequences complementary to SEQ. ID. NOS.: 1, 5 or 23;   (b) nucleotide sequences that hybridize under standard stringent hybridization conditions to one or more of the following nucleotide sequences: SEQ. ID. NOS.: 1, 5, 23 and the respective complements of SEQ. ID. NOS.: 1, 5 and 23; and   (c) nucleotide sequences that but for the degeneracy of the genetic code would hybridize under standard stringent hybridization conditions to one or more of the following nucleotide sequences: SEQ. ID. NOS.: 1, 5, 23 and the respective complements of SEQ. ID. NOS.: 1, 5 and 23.   
     
     
         2 . An isolated nucleic acid according to  claim 1  which encodes an MN protein or polypeptide. 
     
     
         3 . An isolated nucleic acid according to  claim 1  wherein the nucleotide sequence for said nucleic acid is selected from the group consisting of:
 (a) SEQ. ID. NO.: 23 and its complement;   (b) nucleotide sequences that hybridize under standard stringent hybridization conditions to SEQ. ID. NO.: 23 or to its complement; and   (c) nucleotide sequences that but for the degeneracy of the genetic code would hybridize under standard stringent hybridization conditions to SEQ. ID. NO.: 23 or to its complement;   wherein the nucleic acids represented by the nucleotide sequences of (b) and (c) function to identify MN nucleic acid sequences.   
     
     
         4 - 5 . (canceled) 
     
     
         6 . An isolated nucleic acid according to  claim 1  operatively linked to an expression control sequence within a vector. 
     
     
         7 . A unicellular host which is either prokaryotic or eukaryotic that is transformed or transfected with the isolated nucleic acid operatively linked to an expression control sequence in a vector according to  claim 6 . 
     
     
         8 . A unicellular host according to  claim 7  which is an insect cell or an  E. coli  cell. 
     
     
         9 . An MN protein or polypeptide encoded by the isolated nucleic acid according to  claim 2 . 
     
     
         10 . A fusion protein comprising at least a first and a second amino acid wherein the first amino acid is encoded by an isolated nucleic acid according to  claim 2 , and wherein the second amino acid is a non-MN protein or polypeptide. 
     
     
         11 . (canceled) 
     
     
         12 . A method of recombinantly producing an MN protein or polypeptide wherein a baculovirus expression system is used comprising the steps of:
 (a) transforming an appropriate unicellular host with an isolated nucleic acid operatively linked to an expression control sequence in a vector according to  claim 6 ;   (b) culturing said unicellular host so that said MN protein or polypeptide is expressed; and   (c) extracting and isolating said MN protein or polypeptide.   
     
     
         13 . An antibody which specifically binds to an epitope of an MN protein or polypeptide according to  claim 9 . 
     
     
         14 . An antibody according to  claim 13  which is monoclonal. 
     
     
         15 - 16 . (canceled) 
     
     
         17 . An antibody according to  claim 13  which specifically binds to an MN antigen epitope selected from the group of epitopes represented by the following amino acid sequences: SEQ. ID. NOS. 10-16. 
     
     
         18 - 21 . (canceled) 
     
     
         22 . An antibody according to  claim 13  which is linked to a chemotherapeutic agent or a toxic agent. 
     
     
         23 . A method of delivering a chemotherapeutic agent or toxic agent to a cancer cell which comprises contacting said cell with an antibody according to  claim 22 . 
     
     
         24 . An antibody according to  claim 13  which is linked to an imaging agent. 
     
     
         25 . A method of imaging pre-neoplastic or neoplastic disease in a patient comprising:
 (a) injecting said patient with antibody according to  claim 24 ; and   (b) detecting the binding of said antibody.   
     
     
         26 . A method of detecting and/or quantitating in a vertebrate sample MN antigen comprising the steps of:
 (a) contacting said sample with an antibody according to  claim 13 ; and   (b) detecting and/or quantitating binding of said antibody in said sample.   
     
     
         27 . The method according to  claim 26  wherein said detecting and/or quantitating is by immunohistochemical staining. 
     
     
         28 . The method according to  claim 26  which is diagnostic/prognostic for pre-neoplastic/neoplastic disease. 
     
     
         29 . A method of detecting and/or quantitating MN-specific antibodies in a vertebrate sample comprising the steps of:
 (a) contacting and incubating the vertebrate sample with a fusion protein according to  claim 10 ; and   (b) detecting and/or quantitating binding of said fusion protein to antibody in said sample.   
     
     
         30 . (canceled)