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A Novel Model System for Analyzing the Functional Domains of CEACAM1‐4S
Author(s) -
Lawson Erika Lynn,
Hixson Douglas C
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.a179-a
Subject(s) - gene isoform , morphogenesis , biology , cell culture , microbiology and biotechnology , transmembrane protein , phenotype , alternative splicing , cytoplasm , cell , cancer research , clone (java method) , gene , genetics , receptor
CEACAM1‐4L is a multifunctional Ig‐like cell adhesion molecule that is lost in a high percentage of carcinomas in the liver, prostate, colon and bladder. Two isoforms, CEACAM1‐4L and CEACAM1‐4S, produced by differential splicing are predominant in the rat liver. Restoration of CEACAM1‐4L expression has an inhibitory effect on the tumorigenicity of various types of epithelial cancers but co‐expression of the 4S isoform appears to influence the effects of CEACAM1‐4L (Turbide et. al.). CEACAM1‐4S has been shown to induce glandular morphogenesis of breast cancer cells (Kirshner et. al.). These observations suggest that the less well‐characterized 4S isoform transduces signals affecting growth and morphogenesis. We have isolated a non‐tumorigenic clone (253‐NT) of the rat hepatoma cell line, 253T, a cell line that does not express CEACAM1. Our lab has accumulated evidence to suggest that CEACAM1‐4S infection of this non‐tumorigenic cell line allows for reversion to a tumorigenic phenotype. To further our current understanding of how CEACAM1‐4S functions in epithelial cells we are using site‐directed mutagenesis, tumorigenicity assays, and blue native gel electrophoresis to analyze the phosphorylation, dimerization and signaling motifs in the transmembrane and cytoplasmic domains of CEACAM1‐4S. Supported by Grants: F31 CA103372, CA42715, CA93840, and P20RR017695