ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P345

Deregulated Wnt/[beta]-catenin signaling in breast cancer: the LRP5[delta] receptor

Peyman Björklund, Jessica Svedlund, Anna-Karin Olsson, Gunnar Westin & Göran Ækerström

Uppsala University, Uppsala, Sweden.

Background: Aberrant accumulation of cytoplasmic/nuclear β-catenin frequently occurs in breast cancers and breast cancer cell lines. Deregulated expression of Wnt ligands, sFRP1 and Dvl1, but no inactivating or activating mutations in Wnt signaling components have so far been reported. We have recently described an internally truncated LRP5 receptor (LRP5Δ) in 91% of hyperparathyroid tumors, and showed that LRP5Δ was strongly implicated in the aberrant accumulation of active ß-catenin in these tumors (Björklund et al. PLoS Med 2007).

Objectives and methods: We have initially analyzed a small number of primary breast carcinomas (19) and several breast cancer cell lines, as well as normal breast tissue for expression of LRP5Δ. Further, we have investigated function of LRP5Δ in the Wnt/β-catenin signaling pathway and in maintaining tumor cell growth both in vitro and in an in vivo xenograft mice model.

Results: We have found expression of the LRP5Δ receptor in 16 of 19 primary breast carcinomas and in several breast cancer cell lines, including MCF-7. No expression of LRP5Δ was observed in normal breast tissues. Experiments on MCF-7 cells will be presented, strongly supporting a fundamental role of the LRP5Δ receptor in deregulated Wnt/ß-catenin signaling and tumor growth in transplanted SCID mice.

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