PTEN (encoded by Pten) is a DUSP that counters the activity of PI3K.109,110 Inactivation of PTEN in humans and mice has established PTEN as a bona fide tumor suppressor.111,112 At the molecular level, PTEN is primarily responsible for dephosphorylation of the lipid second messenger PtdIns(3,4,5)P3 to counterbalance PI3K upon various stimuli.113,114 Cells of the osteoblastic lineage express both PI3K and PTEN. This evidence concerns the gene PTEN and neoplasm.