SUPPRESSION OF TUMORIGENICITY OF GLIOBLASTOMA CELLS BY ADENOVIRUS-MEDIATED MMAC1 PTEN GENE-TRANSFER/

Mutated in multiple advanced cancers 1/phosphatase and tensin homologu e (MMAIC1/PTEN) is a novel tumor suppressor gene candidate located on chromosome 10 that is commonly mutated in human glioblastoma multiform e and several other cancer types. To evaluate the function of this gen e as a tumor suppressor, we constructed a replication-defective adenov irus (MMCB) for efficient, transient transduction of MMAC1 into tumor cells. Infection of MMAC1-mutated U87MG glioblastoma cells with MMCB r esulted in dose-dependent exogenous MMAC1 protein expression as detect ed by Western blotting of cell lysates. In vitro proliferation of U87M G cells was inhibited by MMCB in comparison to several control adenovi ruses at equal viral doses, implying a specific effect of MMAC1 expres sion. Anchorage-independent growth in soft agar was also inhibited by MMCB compared to control adenovirus. Tumorigenicity in nude mice of tr ansiently transduced mass cell cultures was then assessed. MMCB-infect ed U87MG cells were almost completely nontumorigenic compared to untre ated and several control adenovirus-treated cells at equal viral doses , These data support an in vivo tumor suppression activity of MMAC1/PT EN and suggest that in vivo gene transfer with this recombinant adenov iral vector has a potential use in cancer gene therapy.