Dlc-1 gene deleted in cancers

Abstract

A cDNA molecule corresponding to a newly discovered human gene is disclosed. The new gene, which is frequently deleted in liver cancer cells and cell lines, is called the DLC-1 gene. Because the gene is frequently deleted in liver cancer cells, but present in normal cells, it is thought to act as a tumor suppressor. This gene is also frequently deleted in breast and colon cancers, and its expression is decreased or undetectable in many prostate and colon cancers. Also disclosed is the amino acid sequence of the protein encoded by the DLC-1 gene. Methods of using these biological materials in the diagnosis and treatment of hepatocellular cancer, breast cancer, colon cancer, prostate cancer, and adenocarcinomas are presented.

1 . An isolated nucleic acid molecule selected from the group consisting of:
 (a) nucleic acid molecules encoding an amino acid sequence as shown in Seq. I.D. No. 2;   (b) nucleic acid molecules which hybridize under stringent conditions to a nucleic acid molecule according to (a), and which encode a protein having an activity of the DLC-1 protein;   (c) nucleic acid molecules comprising a nucleotide sequence as shown in Seq. I.D. No. 1.   
     
     
         2 . An isolated nucleic acid molecule according to  claim 1 (b) wherein the DNA molecule hybridizes to a DNA molecule according to (a) under conditions wherein DNA molecules with more than 25% mismatch will not hybridize to each other. 
     
     
         3 . A recombinant vector including a nucleic acid molecule according to  claim 1 . 
     
     
         4 . An isolated nucleic acid molecule comprising at least 15 consecutive nucleotides of a DNA sequence shown in Seq. I.D. No. 1. 
     
     
         5 . An isolated nucleic acid molecule according to  claim 4  wherein the molecule comprises at least 25 consecutive nucleotides of the DNA sequence shown in Seq. I.D. No. 1. 
     
     
         6 . A recombinant DNA vector including a DNA molecule according to  claim 4 . 
     
     
         7 . The purified protein of  claim 15 , wherein the amino acid sequence comprises the sequence specified in 15(a). 
     
     
         8 . An antibody capable of specifically binding to a protein according to  claim 7 . 
     
     
         9 . The antibody of  claim 8  wherein the antibody is a monoclonal antibody. 
     
     
         10 . An isolated cDNA molecule encoding a human DLC-1 protein. 
     
     
         11 . A cDNA according to  claim 10  wherein the cDNA comprises the nucleic acid sequence depicted as bases 325-3657 of Seq. I.D. No. 1. 
     
     
         12 . A cDNA according to  claim 10  wherein the human DLC-1 protein comprises an amino acid sequence as depicted in Seq. I.D. No. 2. 
     
     
         13 . A method of detecting a deletion of a DLC-1 gene in a cell, the method comprising
 (a) incubating an oligonucleotide according to  claim 15  with nucleic acid of the cell under conditions such that the oligonucleotide will specifically hybridize to a DLC-1 gene present in the nucleic acid to form an oligonucleotide:DLC-1 gene complex;   (b) detecting the presence or absence of oligonucleotide:DLC-1 complexes, wherein the absence of said complexes indicates deletion of the DLC-1 gene.   
     
     
         14 . A method of detecting the presence of DLC-1 protein in a cell, the method comprising
 (a) incubating an antibody according to  claim 10  with proteins of the cell under conditions such that the antibody will specifically bind to a DLC-1 protein present in the cell to form an antibody:DLC-1 protein complex; and   (b) detecting the presence of antibody:DLC-1 protein complexes.   
     
     
         15 . A purified protein having DLC-1 protein biological activity, and comprising an amino acid sequence selected from the group of:
 (a) the amino acid sequence shown in Seq. I.D. No.2;   (b) amino acid sequences that differ from those specified in (a) by one or more conservative amino acid substitutions; and   (c) amino acid sequences having at least 90% sequence identity to the sequence specified in (a).   
     
     
         16 . The purified protein of  claim 15 (c), wherein the amino acid sequences have at least 95% sequence identity to the sequence specified in 15(a). 
     
     
         17 . The purified protein of  claim 15 (c), wherein the amino acid sequences have at least 98% sequence identity to the sequence specified in 15(a).