Abstract | BACKGROUND: METHODOLOGY/PRINCIPAL FINDINGS: Caco-2/15, HCT116 and CT26 cells were infected with recombinant lentiviruses expressing a shRNA specifically designed to knock-down PTEN. The impact of PTEN downregulation was analyzed on cell polarization and differentiation, intercellular junction integrity (expression of cell-cell adhesion proteins, barrier function), migration ( wound assay), invasion ( matrigel-coated transwells) and on tumor and metastasis formation in mice. Electron microscopy analysis showed that lentiviral infection of PTEN shRNA significantly inhibited Caco-2/15 cell polarization, functional differentiation and brush border development. A strong reduction in claudin 1, 3, 4 and 8 was also observed as well as a decrease in transepithelial resistance. Loss of PTEN expression increased the spreading, migration and invasion capacities of colorectal cancer cells in vitro. PTEN downregulation also increased tumor size following subcutaneous injection of colorectal cancer cells in nude mice. Finally, loss of PTEN expression in HCT116 and CT26, but not in Caco-2/15, led to an increase in their metastatic potential following tail-vein injections in mice. CONCLUSIONS/SIGNIFICANCE: Altogether, these results indicate that PTEN controls cellular polarity, establishment of cell-cell junctions, paracellular permeability, migration and tumorigenic/metastatic potential of human colorectal cancer cells.
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Authors | Marie-Josée Langlois, Sébastien Bergeron, Gérald Bernatchez, François Boudreau, Caroline Saucier, Nathalie Perreault, Julie C Carrier, Nathalie Rivard |
Journal | PloS one
(PLoS One)
Vol. 5
Issue 12
Pg. e15742
(Dec 23 2010)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21203412
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Caco-2 Cells
- Cell Line, Tumor
- Cell Polarity
- Colorectal Neoplasms
(enzymology)
- Epithelial Cells
(cytology)
- Female
- Gene Expression Regulation, Enzymologic
- Gene Expression Regulation, Neoplastic
- Humans
- Intestines
(enzymology)
- Mice
- Mice, Nude
- Mice, SCID
- PTEN Phosphohydrolase
(metabolism)
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