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Retinol reduces beta‐catenin protein in retinoic acid‐resistant colon cancer cells by increasing beta‐catenin‐RXR‐alpha interaction in the nucleus and translocation into the cytosol
Author(s) -
Dillard Alice C,
Lane Michelle
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a59-c
Subject(s) - retinoic acid , retinol , cytosol , beta catenin , microbiology and biotechnology , retinoid x receptor , chemistry , retinol binding protein , biology , biochemistry , cell culture , transcription factor , signal transduction , wnt signaling pathway , nuclear receptor , vitamin , enzyme , genetics , gene
We previously reported that retinol utilized an RXR‐mediated degradation pathway to decrease beta‐catenin via proteasomal degradation in three all‐trans retinoic acid‐resistant human colon cancer cell lines. The current study elucidates the mechanism by which the RXR‐mediated degradation pathway reduces beta‐catenin protein in response to retinol treatment in these same cell lines. In each cell line, retinol treatment increased beta‐catenin and RXR‐alpha protein interaction at 8 h resulting in a decrease in total beta‐catenin protein at 24 and 48 h. Twenty‐four h of retinol treatment increased RXR‐alpha protein but 48 h of retinol treatment significantly decreased RXR‐alpha protein levels. Treatment with a proteasomal inhibitor blocked the decrease in RXR‐alpha. Retinol treatment also triggered a relocation of beta‐catenin and RXR‐alpha proteins. Cells treated with retinol for 24 h displayed increased cytosolic but decreased nuclear beta‐catenin and RXR‐alpha. These results suggest that retinol induces RXR‐alpha and beta‐catenin binding in the nucleus and their transport to the cytosol where both proteins are proteasomally degraded. This research was funded by the American Cancer Society Research Scholar Grant #RSG‐03‐233‐01‐CNE.