PTEN regulates RANKL- and osteopontin-stimulated signal transduction during osteoclast differentiation and cell motility

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78 Scopus citations

Abstract

PTEN (also known as MMAC-1 or TEP-1) is a frequently mutated tumor suppressor gene in human cancer. PTEN functions have been identified in the regulation of cell survival, growth, adhesion, migration, and invasiveness. Here, we characterize the diverse signaling networks modulated by PTEN in osteoclast precursors stimulated by RANKL and osteopontin (OPN). RANKL dose-dependently stimulated transient activation of Akt before activation of PTEN, consistent with a role for PTEN in decreasing Akt activity. PTEN overexpression blocked RANKL-activated Akt stimulated survival and osteopontin-stimulated cell migration while a dominant-negative PTEN increased the actions of RANKL and OPN. PTEN overexpression suppressed RANKL-mediated osteoclast differentiation and OPN-stimulated cell migration. The PTEN dominant-negative constitutively induced osteoclast differentiation and cell migration. Our data demonstrate multiple roles for PTEN in RANKL-induced osteoclast differentiation and OPN-stimulated cell migration in RAW 264.7 osteoclast precursors.

Original languageEnglish
Pages (from-to)5001-5008
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number7
DOIs
StatePublished - Feb 14 2003

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