Polypeptides and nucleic acids associated with cancer

Abstract

The present invention provides methods, reagents, and kits for diagnosing and treating cancer in a mammal, e.g., a human. This invention is based upon the discovery that G2A, GPR4, GPR65, and OGR1 are overexpressed and/or amplified in cancer. Methods to detect cancer or a propensity to develop cancer, to monitor the efficacy of a cancer treatment, and to treat cancer, by inhibiting the expression and/or activity of G2A, GPR4, GPR65, and OGR1 in a cancer cell are included.

What is claimed is:  
     
         1 . A method of detecting cancer, the method comprising steps of: 
 (i) providing a biological sample from a mammal; and    (ii) detecting an overexpression, in comparison to a control level, of a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:2 or a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:4 or a polypeptide comprising at least 70% amino acid sequence identity to SEQ ID NO:6 or a polypeptide comprising at least 70% amino acid sequence identity to SEQ ID NO:8 in the biological sample, thereby detecting the presence of cancer in the mammal.    
     
     
         2 . The method of  claim 1 , wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:8.  
     
     
         3 . The method of  claim 1 , wherein the polypeptide is detected using an antibody that selectively binds to the polypeptide.  
     
     
         4 . The method of  claim 3 , wherein the polypeptide is quantified by immunoassay.  
     
     
         5 . The method of  claim 1 , wherein the cancer cells are from an epithelial cancer.  
     
     
         6 . The method of  claim 5 , wherein the epithelial cancer is a breast cancer.  
     
     
         7 . The method of  claim 1 , wherein the mammal is a human.  
     
     
         8 . A method of detecting cancer, the method comprising steps of: 
 (i) providing a biological sample from a mammal; and    (ii) detecting an increase in expression, relative to a control level, of a gene encoding a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:2, or a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:4, or a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:6, or a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:8 in the biological sample, thereby detecting the presence of cancer cells in the biological sample.    
     
     
         9 . The method of  claim 8 , wherein the detecting step further comprises: 
 (a) contacting the gene with a probe that selectively hybridizes to the gene under conditions in which the probe selectively hybridizes to the gene to form a stable hybridization complex; and    (b) detecting the hybridization complex.    
     
     
         10 . The method of  claim 8 , wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4, or SEQ ID NO:6, or SEQ ID NO:8.  
     
     
         11 . The method of  claim 1 , wherein the detecting step comprises detecting an mRNA that encodes the polypeptide.  
     
     
         12 . The method of  claim 11 , wherein the mRNA is detected using an amplification reaction.  
     
     
         13 . The method of  claim 8 , wherein the cancer cells are from an epithelial cancer.  
     
     
         14 . The method of  claim 13 , wherein the epithelial cancer is selected from the group consisting of breast cancer, ovarian cancer, prostate cancer, colorectal cancer, and lung cancer.  
     
     
         15 . The method of  claim 8 , wherein the mammal is a human.  
     
     
         16 . A method of monitoring the efficacy of a therapeutic treatment of cancer, the method comprising the steps of: 
 (i) providing a biological sample from a mammal undergoing the therapeutic treatment; and    (ii) detecting a level of a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:2 or a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:4 or a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:6 or a polypeptide comprising at least 70% amino acid identity to SEQ ID NO:8 in the biological sample compared to a level in a biological sample from the mammal prior to, or earlier in, the therapeutic treatment, thereby monitoring the efficacy of the therapy.    
     
     
         17 . The method of  claim 16 , wherein the polypeptide has an amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4 or SEQ ID NO:6 or SEQ ID NO:8.  
     
     
         18 . The method of  claim 16 , wherein the cancer is an epithelial cancer.  
     
     
         19 . The method of  claim 17 , wherein the epithelial cancer is selected from the group consisting of breast cancer, ovarian cancer, prostate cancer, colorectal cancer, and lung cancer.  
     
     
         20 . The method of  claim 16 , wherein the mammal is a human.  
     
     
         21 . A method of inhibiting proliferation of a cancer cell that overexpresses a polypeptide comprising greater than 70% amino acid identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:8, the method comprising the step of contacting the cancer cell with a therapeutically effective amount of an inhibitor of the polypeptide.  
     
     
         22 . The method of  claim 21 , wherein the cancer cell is selected from the group consisting of a breast, ovarian lung, colon, or prostate cancer cell.  
     
     
         23 . The method of  claim 21 , wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:1.  
     
     
         24 . The method of  claim 21 , wherein the inhibitor is an antibody.  
     
     
         25 . The method of  claim 21 , wherein the inhibitor is an antisense polynucleotide.  
     
     
         26 . The method of  claim 21 , wherein the inhibitor is an organic compound.  
     
     
         27 . A method of treating cancer in a mammal that overexpresses a polypeptide comprising greater than 70% amino acid identity to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, or SEQ ID NO:8, the method comprising the step of administering a therapeutically effective amount of an inhibitor of the polypeptide.  
     
     
         28 . The method of  claim 27 , wherein the cancer is selected from the group consisting of a breast, ovarian lung, colon, or prostate cancer.  
     
     
         29 . The method of  claim 27 , wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:1.  
     
     
         30 . The method of  claim 27 , wherein the inhibitor is an antibody.  
     
     
         31 . The method of  claim 27 , wherein the inhibitor is an antisense polynucleotide.  
     
     
         32 . The method of  claim 27 , wherein the inhibitor is an organic compound.