NSP molecules

Abstract

The present invention relates to nucleotide sequences, including expressed sequence tags (ESTs), oligonucleotide probes, polypeptides, antagonists and agonists vectors and host cells expressing, and immunoadhesions and antibodies to PRO201, PRO308 or PRO309 polypeptides. The invention further relates to compositions and method for the diagnosis and treatment of neoplastic cell growth and proliferation in mammals, including humans. The invention is based in part on the identification of genes that are amplified in the genome of tumor cells. Such gene amplification is expected to be associated with the overexpression of the gene product and contribute to tumorigenesis. Accordingly, the proteins encoded by the amplified genes are believed to be useful targents for the diagnosis and/or treatment (including prevention) of certain tumors (e.g., cancer) and may act as predictors of the prognosis of tumor treatment.

What is claimed is:  
     
         1 . Isolated nucleic acid comprising DNA having at least a 90% sequence identity to (a) a DNA molecule encoding a PRO201 polypeptide comprising the sequence of amino acids 1 to 576 of FIG. 1 (SEQ ID NO:1), or (b) the complement of the DNA molecule of (a).  
     
     
         2 . The isolated nucleic acid comprising DNA having at least a 90% sequence identity to (a) a DNA molecule encoding a PRO309 polypeptide comprising the sequence of amino acids 1 to 703 of FIG. 3 (SEQ ID NO:5), or (b) the complement of the DNA molecule of (a).  
     
     
         3 . The isolated nucleic acid of  claim 1  comprising DNA encoding a PRO201 polypeptide having amino acid residues 1 to 576 of FIG. 1 (SEQ ID NO:1).  
     
     
         4 . The isolated nucleic acid of  claim 2  comprising DNA encoding a PRO309 polypeptide having amino acid residues 1 to 703 of FIG. 3 (SEQ ID NO:5).  
     
     
         5 . An isolated nucleic acid comprising DNA having at least a 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the cDNA in ATCC Deposit No. 209567 (designation: DNA30676-1223), or (b) the complement of the DNA molecule of (a).  
     
     
         6 . An isolated nucleic acid comprising DNA having at least a 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the cDNA in ATCC Deposit No. 209713, or (b) the complement of the DNA molecule of (a).  
     
     
         7 . A vector comprising the nucleic acid of  claim 1 .  
     
     
         8 . A vector comprising the nucleic acid of  claim 2 .  
     
     
         9 . The vector of  claim 7  operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         10 . The vector of  claim 8  operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         11 . A host cell comprising the vector of  claim 9 .  
     
     
         12 . A host cell comprising the vector of  claim 10 .  
     
     
         13 . The host cell of  claim 11  wherein said cell is mammalian.  
     
     
         14 . The host cell of  claim 13  wherein said cell is a CHO cell.  
     
     
         15 . The host cell of  claim 11  wherein said cell is prokaryotic.  
     
     
         16 . The host cell of  claim 15  wherein said cell is an  E. coli.    
     
     
         17 . The host cell of  claim 11  wherein said cell is a yeast cell.  
     
     
         18 . The host cell of  claim 17  wherein said cell is  Saccharomyces cerevisiae.    
     
     
         19 . A process for producing PRO201, PRO308 or PRO309 polypeptides comprising culturing the host cell of  claim 6  under conditions suitable for expression of PRO201, PRO308 or PRO309, respectively, and recovering PRO201, PRO308 or PRO309, respectively, from the cell culture.  
     
     
         20 . Isolated native sequence PRO201 polypeptide comprising amino acid residues 1 to 576 of FIG. 1 (SEQ ID NO:1).  
     
     
         21 . Isolated native sequence PRO309 polypeptide comprising amino acid residues 1 to 703 of FIG. 3 (SEQ ID NO:5).  
     
     
         22 . Isolated native sequence PRO201 polypeptide encoded by the nucleotide deposited under accession number ATCC 209567.  
     
     
         23 . Isolated native sequence PRO309 polypeptide encoded by the nucleotide deposited under accession number ATCC 209713.  
     
     
         24 . A chimeric molecule comprising PRO201, PRO308 or PRO309 polypeptide fused to a heterologous amino acid sequence.  
     
     
         25 . The chimeric molecule of  claim 24  wherein said heterologous amino acid sequence is an epitope tag sequence.  
     
     
         26 . The chimeric molecule of  claim 25  wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin.  
     
     
         27 . An antagonist of Nsp1 (SEQ ID NO:1), Nsp2 (SEQ ID NO:3) or Nsp3 (SEQ ID NO:5) which blocks, prevents, inhibits and/or otherwise neutralizes the normal functioning of Nsp1 (SEQ ID NO:1), Nsp2 (SEQ ID NO:3) or Nsp3 (SEQ ID NO:5), respectively, in cellular signaling.  
     
     
         28 . The antagonist of  claim 27  which is a small bioorganic molecule.  
     
     
         29 . The antagonist of  claim 28  which is an antisense oligonucleotide.  
     
     
         30 . An antibody which specifically binds to PRO201, PRO308 or PRO309 polypeptide.  
     
     
         31 . The antibody of  claim 30  wherein said antibody is a monoclonal antibody.  
     
     
         32 . The antibody of  claim 31  which induces the death of a cell overexpressing PRO201, PRO308 or PRO309 polypeptide.  
     
     
         33 . The antibody of  claim 32  wherein said cell is a tumor cell.  
     
     
         34 . The antibody of  claim 31  which is labeled.  
     
     
         35 . The antibody of  claim 34  which is immobilized on a solid support.  
     
     
         36 . The antibody of  claim 34  which is an active fragment, single-chain antibody or an anti-idiotypic antibody.  
     
     
         37 . A composition comprising an antibody of  claim 30  in admixture with a pharmaceutically acceptable carrier.  
     
     
         38 . The composition of  claim 37  comprising a growth inhibitory amount of said antibody.  
     
     
         39 . The composition of  claim 38  further comprising a second antibody or a cytotoxic or chemotherapeutic agent.  
     
     
         40 . A method for determining the presence of a PRO201, PRO308 or PRO309 polypeptide comprising exposing a cell suspected of containing PRO201, PRO308 or PRO309 or expressing DNA encoding said polypeptide to anti-PRO201, anti-PRO308 or anti-PRO309 and determining the binding of said antibody to said cell.  
     
     
         41 . A method of diagnosing tumor in a mammal, comprising detecting the level of expression of a gene encoding a PRO201, PRO308 or PRO309 polypeptide (a) in a test sample of tissue cells obtained from the mammal, and (b) in a control sample of known normal tissue cells of the same cell type, wherein a higher expression level in the test sample indicated the presence of tumor in the mammal from which the test tissue cells were obtained.  
     
     
         42 . A method of diagnosing tumor in a mammal, comprising (a) contacting a anti-PRO201, anti-PRO308 or anti-PRO309 antibody with a test sample of tissue cells obtained from the mammal, and (b) detecting the formation of a complex between the anti-PRO201, anti-PRO308 or anti-PRO309 antibody and the PRO201, PRO308 or PRO309 polypeptide in the test sample.  
     
     
         43 . The method of  claim 42  wherein said test sample is obtained from a mammal suspected to have neoplastic cell growth or proliferation.  
     
     
         44 . A cancer diagnostic kit, comprising an anti-PRO201, anti-PRO308 or anti-PRO309 antibody and a carrier in suitable packaging.  
     
     
         45 . A method for inhibiting the growth of tumor cells comprising exposing a cell which overexpresses a PRO201, PRO308 or PRO309 polypeptide to an effective amount of an agent inhibiting the expression and/or activity of the PRO201, PRO308 or PRO309 polypeptide.  
     
     
         46 . The method of  claim 45 , wherein said agent is an anti-PRO201, anti-PRO308 or anti-PRO309 antibody.  
     
     
         47 . The method of  claim 46  wherein said tumor cells are further exposed to radiation treatment or a cytotoxic or chemotherapeutic agent.