Mutations in the tumor suppressor gene PTEN (MMAC1/TEP1) are associated wit
h a large number of human cancers and several autosomal-dominant disorders.
Mice mutant for PTEN die at early embryonic stages and the mutant embryoni
c fibroblasts display decreased sensitivity to cell death. Overexpression o
f PTEN in different mammalian tissue culture cells affects various processe
s including cell proliferation, cell death and cell migration. We have char
acterized the Drosophila PTEN gene and present evidence that both inactivat
ion and overespression of PTEN affect cell size, while overexpression of PT
EN also inhibits cell cycle progression at early mitosis and promotes cell
death during eye development in a context-dependent manner. Furthermore, we
have shown that PTEN acts in the insulin signaling pathway and all signals
from the insulin receptor can be antagonized by either Drosophila or human
PTEN, suggesting a potential means for alleviating symptoms associated wit
h altered insulin signaling.