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Retinoblastoma suppressor associated protein 46 (RbAp46) attenuates the beta-catenin/TCF signaling through up-regulation of GSK-3beta expression.

BACKGROUND
BETA-Catenin plays a critical role in embryonic development and tumorigenesis through its function in cell-cell adhesion and in the Wnt-dependent signaling pathway. Thus, the expression of this important protein is strictly and dynamically regulated.


MATERIALS AND METHODS
A stable cell line from mammary epithelial cells MCF10AT3B that ectropically expresses the retinoblastoma suppressor (Rb) associated protein 46 (RbAp46) was established, and used Western blot, luciferase and cell growth assays to study the effects of constitutive RbAp46 expression.


RESULTS
MCF10AT3B cells expressing recombinant RbAp46 exhibited a decreased rate of cell growth. In RbAp46-expressing cells, betacatenin protein was highly phosphorylated and the steady state levels of beta-catenin protein were significantly decreased. Accordingly, the beta-catenin/TCF nuclear signaling was dramatically reduced in RbAp46 expressing cells. In addition, expression levels of glycogen synthase kinase-3beta (GSK-3beta) were increased in RbAp46 expressing cells.


CONCLUSION
RbAp46 plays an important role in regulation of beta-catenin expression and the beta-catenin/TCF signaling pathway presumably through regulation of GSK-3beta expression.