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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2011;4(4):299-308
Original Article
Differentiated intestinal epithelial cells express high levels of TGF-β receptors and
exhibit increased sensitivity to growth inhibition
Navneeta Rathor, Shelley R Wang, Elizabeth T Chang, Jaladanki N Rao
Cell Biology Group, Department of Surgery, University of Maryland School of Medicine; Baltimore Veterans Affairs Medical Center,
Baltimore, MD 21201, USA.
Received October 8, 2011; November 5, 2011; Epub November 10, 2011; Published November 30, 2011
Abstract: Background: Intestinal epithelial cells (IECs) within crypts continuously divide and differentiate as they migrate up towards the
luminal surface of the mucosa. With the onset of differentiation, IECs lose their proliferative potential, but the exact mechanism remains
unknown. This current study examined the involvement of the TGF-β signaling pathway in this process. Methods: Studies were
conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Cell differentiation was induced by forced expression of the
Cdx2 gene, a transcription factor responsible for controlling intestinal epithelial cell differentiation. Results: Forced expression of the
Cdx2 gene in stable Cdx2-transfected IEC-6 cells resulted in a differentiated phenotype as indicated by morphological features and
increased expression of sucrase-isomaltase. Levels of TGF-β type I receptor (TGFβ-RI) and TGF-β type II receptor (TGFβ-RII) increased
in these differentiated epithelial cells. The induced TGFβ-RI and TGFβ-RII expression in Cdx2-transfected IEC-6 cells was associated
with increased sensitivity to TGF-β-induced growth inhibition. Depletion of cellular polyamines further increased TGF-β receptor
expression and additionally enhanced the response to TGF-β-induced growth inhibition. Increased TGFβ-RI and RII in polyamine-
deficient cells were also associated with an induction in JunD/AP-1 activity. Conclusions: These results indicate that the loss of the
proliferative potential in differentiated IECs results partially from the increased expression of TGF-β receptors. (IJCEM1110002).
Key words: Cdx2 gene, intestinal epithelium, TGF-β Receptors, AP-1 binding sites, cell growth, electrophoretic mobility shift assay,
supershift assays
Full Text PDF
Address all correspondence to:
Dr. Jaladanki N Rao
Department of Surgery
University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center
10 North Greene Street, Baltimore, MD 21201, USA.
Tel: 410-605-7808; Fax: 410-605-7949
E-mail: jrao@umaryland.edu
Original Article
Differentiated intestinal epithelial cells express high levels of TGF-β receptors and
exhibit increased sensitivity to growth inhibition
Navneeta Rathor, Shelley R Wang, Elizabeth T Chang, Jaladanki N Rao
Cell Biology Group, Department of Surgery, University of Maryland School of Medicine; Baltimore Veterans Affairs Medical Center,
Baltimore, MD 21201, USA.
Received October 8, 2011; November 5, 2011; Epub November 10, 2011; Published November 30, 2011
Abstract: Background: Intestinal epithelial cells (IECs) within crypts continuously divide and differentiate as they migrate up towards the
luminal surface of the mucosa. With the onset of differentiation, IECs lose their proliferative potential, but the exact mechanism remains
unknown. This current study examined the involvement of the TGF-β signaling pathway in this process. Methods: Studies were
conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Cell differentiation was induced by forced expression of the
Cdx2 gene, a transcription factor responsible for controlling intestinal epithelial cell differentiation. Results: Forced expression of the
Cdx2 gene in stable Cdx2-transfected IEC-6 cells resulted in a differentiated phenotype as indicated by morphological features and
increased expression of sucrase-isomaltase. Levels of TGF-β type I receptor (TGFβ-RI) and TGF-β type II receptor (TGFβ-RII) increased
in these differentiated epithelial cells. The induced TGFβ-RI and TGFβ-RII expression in Cdx2-transfected IEC-6 cells was associated
with increased sensitivity to TGF-β-induced growth inhibition. Depletion of cellular polyamines further increased TGF-β receptor
expression and additionally enhanced the response to TGF-β-induced growth inhibition. Increased TGFβ-RI and RII in polyamine-
deficient cells were also associated with an induction in JunD/AP-1 activity. Conclusions: These results indicate that the loss of the
proliferative potential in differentiated IECs results partially from the increased expression of TGF-β receptors. (IJCEM1110002).
Key words: Cdx2 gene, intestinal epithelium, TGF-β Receptors, AP-1 binding sites, cell growth, electrophoretic mobility shift assay,
supershift assays
Full Text PDF
Address all correspondence to:
Dr. Jaladanki N Rao
Department of Surgery
University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center
10 North Greene Street, Baltimore, MD 21201, USA.
Tel: 410-605-7808; Fax: 410-605-7949
E-mail: jrao@umaryland.edu
