[Overexpression of human homeobox gene in lung cancer A549 cells results in enhanced motile and invasive properties].

Since homeobox-containing genes (HOX genes) are a family of transcriptional regulators, which give cells positional information in morphogenesis, cancer metastasis can be explained as a heterotopic expression of HOX genes. In the present study, I transfected HOXD3 gene into human lung cancer A549 cells and investigated alterations of adhesiveness, migration and invasiveness of the tumor cells. Overexpression of the HOXD3 gene enhanced expressions of integrin alpha 3, alpha 4 and beta 3 subunits, and increased adhesive and migratory activities toward fibronectin and vitronectin. It was suggested that the increased migration of the tumor cells resulted from enhanced expression and activation of integrin alpha v beta 3. Furthermore, the overexpression of HOXD3 increased mRNA expressions of urokinase-type plasminogen activator and transcription factors ets-1 and -2. Most of these molecules, which increased with overexpression of HOXD3, are well-known factors associated with tumor invasion and metastasis. Indeed, HOXD3 transfectants revealed high invasive activity to matrigel, a basement membrane model, compared to their parent cells and control neo-transfectants. These findings suggest that abnormal expression of HOXD3 may enhance tumor invasion and metastasis through increased expressions of metastasis-related genes.