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Elucidating the mechanism of vitamin A uptake in tumor‐prone, vitamin A‐sensitive tissues
Author(s) -
Schulte Christina Elaine
Publication year - 2010
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.24.1_supplement.716.7
Subject(s) - retinol , retinoic acid , microbiology and biotechnology , vitamin , gene knockdown , retinol binding protein , retinoid , biology , chemistry , biochemistry , apoptosis , gene
Vitamin A (retinol) is not only essential for maintaining normal eye, brain, placenta, and skin function, but its active derivatives have powerful effects on cell proliferation and differentiation. The long‐term goal of this study is to understand how cancer incidence can be reduced through the optimization of vitamin A trafficking and signaling in tissues prone to tumor development. Retinol, the major circulating retinoid, travels to peripheral tissues in complex with retinol binding protein (RBP). Recently, a retinoic acid responsive protein with no known biological function, STRA6, has been identified as an essential transmembrane receptor that mediates retinol uptake in retinal epithelial cells. It conferred RBP binding to retinal cells transfected with a STRA6 expression vector, as well as increased cellular uptake of vitamin A. The goal of our current study is to examine the mechanism of RBP‐bound retinol uptake in mammary, prostate, and colon epithelial cells, which express abundant levels of STRA6. We will utilize siRNA to determine whether knockdown of STRA6 inhibits retinol‐RBP uptake as assessed by tracer assays and fluorescent microscopy, as well as the requirement of STRA6 for retinol‐mediated differentiation, apoptosis, and cell cycle arrest. These studies will lay the foundation for developing strategies for optimizing vitamin A status and retinol trafficking in tissues prone to tumors. Grant Funding Source : NIH SR03CA128091‐0