Restoration of wild-type PTEN expression leads to apoptosis, induces differentiation, and reduces telomerase activity in human glioma cells

PTEN is a candidate tumor suppressor gene identified on human chromosome 10 q23.3 that is frequently mutated or deleted in 30% to 44% of glioblastomas. Transient expression study of PTEN in glioma cells indicates that PTEN pla ys an important role in cellular proliferation, tumorigenicity, cell migrat ion, and focal adhesions. In this study, we examined the biological consequ ences on U87MG glioma cells after stable gene transfer of wild-type PTEN. C ells stably expressing wildtype PTEN protein were found to have suppressed proliferation, as determined by cell counting and Ki-67 staining, as well a s inhibited anchorage-independent growth. The PTEN-expressing cells also sh owed higher expression of glial fibrillary acidic protein and changed morph ologically from spindle-shaped to elongated cell bodies with multiple slend er processes, suggesting that these cells have undergone differentiation. I n addition, telomerase activity decreased more than 10-fold in PTEN-express ing cells when compared with control cells. More importantly, apoptosis was detected in about 5% of PTEN-expressing cells, representing a 17-fold (p < 0.01) increase over the control cells. Taken together, these results sugge st that PTEN plays an important role in regulation of cell homeostasis by m aintaining a balance between proliferation, differentiation, and apoptosis.