Novel stra6 polypeptides

Abstract

The present invention is directed to novel polypeptides having sequence similarity to Stra6, a murine retinoic acid responsive protein, and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

1 - 67 . (canceled) 
     
     
         68 . A method for inhibiting growth of tumor cells, said method comprising exposing tumor cells that express a Stra6 polypeptide to an effective amount of an agent that inhibits a biological activity of said polypeptide, wherein growth of said tumor cells is thereby inhibited. 
     
     
         69 . The method of  claim 68 , wherein said tumor cells over-express said Stra6 polypeptide as compared to normal cells of the same tissue type. 
     
     
         70 . The method of  claim 68 , wherein said agent is an anti-Stra6 antibody or fragment thereof. 
     
     
         71 . The method of  claim 70 , wherein said anti-Stra6 antibody or fragment thereof induces cell death. 
     
     
         72 . The method of  claim 68 , wherein said tumor cells are further exposed to radiation treatment, a cytotoxic agent, or a chemotherapeutic agent. 
     
     
         73 . The method of  claim 68 , wherein said tumor cells are further exposed to an agent that stimulates the expression of Stra6 polypeptide by said tumor cells. 
     
     
         74 . The method of  claim 110 , wherein said retinoid is retinoic acid or an analogue thereof. 
     
     
         75 . The method of  claim 73 , wherein said agent is an antisense oligonucleotide that hybridizes to a nucleic acid which encodes the Stra6 polypeptide or the complement thereof. 
     
     
         76 . The method of  claim 75 , wherein said tumor cells are further exposed to radiation treatment, a cytotoxic agent, or a chemotherapeutic agent. 
     
     
         77 . The method of  claim 75 , wherein said tumor cells are further exposed to an agent that stimulates the expression of the nucleic acid encoding Stra6 polypeptide. 
     
     
         78 . The method of  claim 111 , wherein said retinoid is retinoic acid or an analogue thereof. 
     
     
         79 - 95 . (canceled) 
     
     
         96 . The method of  claim 70 , wherein said antibody comprises a single-chain antibody, a diabody, a linear antibody, or a fragment thereof. 
     
     
         97 . The method of  claim 70 , wherein said antibody is humanized. 
     
     
         98 . The method of  claim 70 , wherein said antibody is monoclonal. 
     
     
         99 . The method of  claim 70 , wherein said antibody fragment comprises a Fab, Fab′, F(ab′) 2 , or Fv fragment. 
     
     
         100 . The method of  claim 70 , wherein said antibody or fragment thereof specifically binds to a Stra6 polypeptide having an extracellular domain comprising the amino acid sequence of amino acid 229 to 295 or 532 to 667 of SEQ ID NO:2. 
     
     
         101 . The method of  claim 70 , wherein said antibody or fragment thereof specifically bind to an extracellular domain of Stra6 polypeptide, the extracellular domain comprising the amino acid sequence of amino acids 229 to 295 or 532 to 667 of SEQ ID NO:2. 
     
     
         102 . The method of  claim 70 , wherein said antibody was raised against amino acid residues 229 to 295 or 532 to 667 of SEQ ID NO:2. 
     
     
         103 . The method of  claim 70 , wherein said antibody or fragment thereof is conjugated to a cytotoxic agent or a prodrug activating agent. 
     
     
         104 . The method of  claim 68 , wherein said Stra6 polypeptide comprises an extracellular domain having the amino acid sequence of amino acids 229 to 295 or 532 to 667 of SEQ ID NO:2. 
     
     
         105 . The method of  claim 68 , wherein said Stra6 polypeptide comprises at least about 95% sequence identity to the sequence of amino acid residues 1 to 667 of SEQ ID NO:2 or 1 to 658 of SEQ ID NO:5. 
     
     
         106 . The method of  claim 68 , wherein said Stra6 polypeptide comprises at least about 99% sequence identity to the sequence of amino acid residues 1 to 667 of SEQ ID NO:2 or 1 to 658 of SEQ ID NO:5. 
     
     
         107 . The method of  claim 75 , wherein said nucleic acid encodes a Stra6 polypeptide having an extracellular domain comprising the amino acid sequence of amino acids 229 to 295 or 532 to 667 of SEQ ID NO:2. 
     
     
         108 . The method of  claim 75 , wherein said nucleic acid encodes a Stra6 polypeptide having at least 95% identity to the sequence of amino acid residues 1 to 667 of SEQ ID NO:2 or 1 to 658 of SEQ ID NO:5. 
     
     
         109 . The method of  claim 75 , wherein said nucleic acid comprises at least 900 nucleotides and hybridizes under stringent hybridization conditions to the complement of the nucleic acid coding sequence that encodes amino acids 1 to 667 of SEQ ID NO:2. 
     
     
         110 . The method of  claim 74 , wherein said agent is a retinoid. 
     
     
         111 . The method of  claim 77 , wherein said agent is a retinoid. 
     
     
         112 . A method of treating a tumor in a subject wherein the tumor cells express Stra6 polypeptide or have a genetic defect in the Wnt-1 pathway, comprising administering to the subject an effective amount of an anti-Stra6 antibody. 
     
     
         113 . The method of  claim 112 , wherein the genetic defect results in abnormal activation of beta-catenin signaling. 
     
     
         114 . The method of  claim 112 , wherein the tumor cells contain a mutation of the APC tumor suppressor of beta-catenin. 
     
     
         115 . The method of  claim 112 , wherein the tumor comprises a breast, lung, colorectal, ovary, endometrium, kidney, melanoma, or pheochromocytome tumor. 
     
     
         116 . The method of  claim 112 , further comprising administering a retinoid or analogue thereof to the subject. 
     
     
         117 . The method of  claim 116 , wherein the retinoid stimulates or enhances overexpression of Stra6 polypeptide by the tumor cells. 
     
     
         118 . The method of  claim 116 , wherein the retinoid is retinoic acid or an analogue thereof. 
     
     
         119 . The method of  claim 112 , wherein the antibody induces tumor cell death. 
     
     
         120 . The method of  claim 112 , wherein the antibody is conjugated to a cytotoxic agent or a prodrug activating agent. 
     
     
         121 . The method  claim 112 , further comprising administering to the subject a cytotoxic agent or chemotherapeutic agent. 
     
     
         122 . The method of  claim 112 , further comprising radiation treatment of the tumor.