Department of Regenerative Medicine and Cell biology

Research in Focus

Akt3: A New Regulator of Tumor Angiogenesis

Akt1, Akt2 and Akt3 are members of a family of serine threonine kinases. Akt1 and Akt2 are regulators of tumorigenesis, however, a role for Akt3 in tumorigenesis is not well established. Researchers in the laboratory of Dr. Robin Muise-Helmericks have found that in ovarian carcinoma, Akt3 regulates the secretion of the angiogenic factor, VEGF. Using a xenograft SCID mouse model they show that Akt3 silencing results in reduced VEGF secretion as well as reduced growth and vascularization of tumors. Furthermore, they have also identified two potential mediators of this Akt3 effect: the tumor cell marker RCAS1 and the cAMP phosphodiesterase, PDE4D5. They show that Akt3 controls the expression of RCAS-1 which is required downstream of Akt3 for the secretion of VEGF. In addition, they show that Akt3 is localized to the endoplasmic reticulum (ER) where it associates with the cyclic AMP-dependent phosphodiesterase, PDE4D5. PDEs are a family of proteins responsible for the specific turnover of cAMP. The cellular localization of different PDE family members is controlled by protein association, allowing for the shuttling of PDE to different cellular compartments and controlling compartment-specific cAMP turnover. Together, the findings suggest that Akt3 is a key regulator of angiogenesis, activating tumor specific pathways controlling growth factor secretion and endothelial specific pathways required for the growth factor response. rif3

posted 9/28/2011

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