The PTEN tumor suppressor inhibits human airway smooth muscle cell migration.

Airway remodeling in asthma is characterized by increased airway smooth muscle (ASM) mass, accompanied by cell migration. It is well known that the proliferation and migration of ASM cells (ASMCs) play a key role in airway remodeling, but the precise mechanism modulating these cellular events remains unclear. One of the genes most likely to be involved in this process is the phosphatase and tensin homolog (PTEN) gene, whose deletion from chromosome 10 can inhibit the proliferation and migration of many cell types. In this study, we investigated the effects of PTEN on human ASMCs. The cells were infected with recombinant adenovirus containing wild-type PTEN cDNA (Ad-PTEN), and the results were compared with those from the uninfected cells and those infected with the GFP-labeled adenovirus vector. Cell proliferation was measured using the MTT method. Cell migration was determined by wound-healing and transwell assays. The expressions of PTEN, phospho-Akt, Akt, phospho-ERK1/2, ERK1/2, phospho-focal adhesion kinase (FAK) and FAK, were examined by Western blot analysis. The results show that PTEN is expressed endogenously in ASMCs, and that Ad-PTEN inhibits the proliferation and migration of these cells. In addition, the Ad-PTEN treatment decreased the phosphorylation of Akt and FAK but not that of ERK1/2. In conclusion, this study demonstrates that PTEN overexpression inhibits the proliferation and migration of human ASMCs by down-regulating the activity of the Akt and FAK signaling pathways.