Basic–Alimentary TractCDX2 regulates liver intestine–cadherin expression in normal and malignant colon epithelium and intestinal metaplasia*,**
Section snippets
Plasmids
A full-length, wild-type CDX2 allele was amplified by polymerase chain reaction (PCR) using hexamer-primed complementary DNA (cDNA) from normal human colon tissue as a template. The CDX2 allele was inserted into the multiple cloning site of the retroviral expression vector pPGS-CMV-CITE-neo (pPGS-neo; provided by G. Nabal, National Institutes of Health, Bethesda, MD), generating the vector pPGS-CDX2. The full-length, wild-type CDX2 allele was also subcloned into the retroviral vector
CDX2 and LI-cadherin expression are tightly correlated in colon carcinoma cells
Like several other human colorectal cancer cell lines, the HT-29 line shows minimal levels of endogenous CDX2 expression.17 To identify candidate CDX2-regulated genes, we generated a polyclonal population of HT-29 colorectal cancer cells expressing high levels of CDX2 by infection of the cells with replication-defective retroviruses carrying a full-length human CDX2 cDNA (Figure 1A).
Discussion
There is now a considerable body of data supporting the notion that the intestine-specific homeobox transcription factor CDX2 has a crucial role in directing intestinal epithelial development and differentiation (reviewed by Silberg et al.).1 However, the means by which it does so remain poorly defined. Presumably, the ability of CDX2 to regulate expression of downstream target genes is crucial in its function in intestinal cell fate specification. To date, only a very limited number of
Acknowledgements
The authors thank A. Friedman, G. Nabel, G. Nolan, J. Wang, and M. M. Taketo for generously providing reagents for the studies described as well as Dr. David Misek for assistance with microarray data.
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Cited by (0)
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Supported by National Institutes of Health grants CA82223, CA84953, and DK58771.
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Address requests for reprints to: Eric R. Fearon, M.D., Ph.D., Division of Molecular Medicine and Genetics, University of Michigan Medical Center, 4301 MSRB III, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109. e-mail: [email protected]; fax: (734) 647-7979.