Methods of use of a novel lysyl oxidase-related protein

Abstract

Novel Lor-2 polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length Lor-2 proteins, the invention further provides isolated Lor-2 fusion proteins, antigenic peptides and anti-Lor-2 antibodies. The invention also provides Lor-2 nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a Lor-2 gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

What is claimed:  
     
         1 . An isolated nucleic acid molecule selected from the group consisting of: 
 a) a nucleic acid molecule comprising a nucleotide sequence which is at least 89% homologous to a nucleotide sequence of SEQ ID NO:1, or a complement thereof;    b) a nucleic acid molecule comprising a fragment of at least 250 nucleotides of a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, or a complement thereof;    c) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence at least about 93% homologous to the amino acid sequence of SEQ ID NO:2;    d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acid residues of the amino acid sequence of SEQ ID NO:2;    e) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the nucleic acid molecule hybridizes to a complement of a nucleic acid molecule comprising SEQ ID NO:1, under stringent conditions;    f) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, or a complement thereof; and    g) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2.    
     
     
         2 . A vector which contains the nucleic acid molecule of  claim 1 .  
     
     
         3 . A host cell which contains the nucleic acid molecule of  claim 1 .  
     
     
         4 . An isolated polypeptide selected from the group consisting of: 
 a) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;    c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 89% homologous to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1;    d) a polypeptide comprising an amino acid sequence which is at least 93% homologous to the amino acid sequence of SEQ ID NO:2; and    e) a polypeptide comprising the amino acid sequence of SEQ ID NO:2.    
     
     
         5 . An antibody which selectively binds to a polypeptide of  claim 4 .  
     
     
         6 . A method for producing a polypeptide selected from the group consisting of: 
 a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;    b) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2 wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2; and    c) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a complement of a nucleic acid molecule comprising SEQ ID NO:1 under stringent conditions;    comprising culturing the host cell of  claim 3  under conditions in which the nucleic acid molecule is expressed.    
     
     
         7 . A method for detecting the presence of a polypeptide of  claim 4  in a sample comprising: 
 a) contacting the sample with a compound which selectively binds to the polypeptide; and  
 b) determining whether the compound binds to the polypeptide in the sample to thereby detect the presence of a polypeptide of  claim 4  in the sample.  
 
     
     
         8 . A kit comprising a compound which selectively binds to a polypeptide of  claim 4  and instructions for use.  
     
     
         9 . A method for detecting the presence of a nucleic acid molecule in  claim 1  in a sample comprising: 
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and  
 b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample to thereby detect the presence of a nucleic acid molecule of  claim 1  in the sample.  
 
     
     
         10 . The method of  claim 9 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.  
     
     
         11 . The method of  claim 9 , wherein the sample is isolated from a sample selected from the group consisting of prostate tissue, liver tissue, breast tissue, skeletal muscle tissue, brain tissue, colon tissue, heart tissue, ovarian tissue, kidney tissue, lung tissue, vascular tissue, aortic tissue, thyroid tissue, placental tissue, intestinal tissue, cervical tissue, splenic tissue, esophageal tissue, thymic tissue, tonsillar tissue, lymph nodes and osteogenic cells.  
     
     
         12 . The method of  claim 9 , wherein the sample is a tumor sample.  
     
     
         13 . A method for diagnosis of a subject with a tumor comprising: 
 contacting a tumor sample from the subject with an agent capable of detecting Lor-2 protein or mRNA;    determining the amount of Lor-2 protein or mRNA expressed in the tumor sample; and    forming a diagnosis based on the amount of Lor2 protein or mRNA expressed in the tumor sample.    
     
     
         14 . A method for determining the metastatic potential of a tumor from a subject comprising: 
 contacting a tumor sample from the subject with an agent capable of detecting Lor-2 protein or mRNA;    determining the amount of Lor-2 protein or mRNA expressed in the tumor sample; and    forming a determination based on the amount of Lor2 protein or mRNA expressed in the tumor sample.    
     
     
         15 . The method of  claim 13  or 14, wherein the tumor sample is selected from the group consisting of a lung tumor, a breast tumor, and a cervical tumor.  
     
     
         16 . A prognostic method comprising: 
 contacting a biological sample from a subject with an agent capable of detecting Lor-2 protein or mRNA;    determining the amount of Lor-2 protein or mRNA expressed in the biological sample; and    forming a prognosis based on the amount of Lor-2 protein or mRNA expressed in the tumor sample.    
     
     
         17 . The method of any of claims  13 ,  14  or  16  further comprising: 
 comparing the amount of Lor-2 protein or mRNA expressed in the biological or tumor sample to a control sample; and  
 forming the diagnosis, determination or prognosis based on the amount of Lor-2 protein or mRNA expressed in the biological or tumor sample as compared to the control sample.  
 
     
     
         18 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         19 . A method for identifying a compound which binds to a polypeptide of  claim 4  comprising: 
 a) contacting the polypeptide, or a cell expressing the polypeptide with a test compound; and  
 b) determining whether the polypeptide binds to the test compound.  
 
     
     
         20 . The method of  claim 19 , wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of: 
 a) detection of binding by direct detection of test compound/polypeptide binding;    b) detection of binding using a competition binding assay; and    c) detection of binding using an assay for Lor-2 activity.    
     
     
         21 . A method of modulating the activity of a polypeptide of  claim 4  comprising contacting the polypeptide or a cell expressing the polypeptide with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         22 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 4  comprising: 
 a) contacting a polypeptide of  claim 4  with a test compound; and  
 b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.  
 
     
     
         23 . A method of regulating metastasis in an individual comprising administering to the individual a Lor-2 modulator such that metastasis is regulated.  
     
     
         24 . The method of  claim 23 , wherein the Lor-2 modulator is a Lor-2 inhibitor.  
     
     
         25 . A method of inhibiting tumor progression in an individual comprising administering to the individual a Lor-2 inhibitor such that tumor progression is inhibited.