Parallels between global transcriptional programs of polarizing Caco-2 intestinal epithelial cells in vitro and gene expression programs in normal colon and colon cancer.
Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell-cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell-cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2.
Sääf
Annika M
AM
Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Halbleib
Jennifer M
JM
Chen
Xin
X
Yuen
Siu Tsan
ST
Leung
Suet Yi
SY
Nelson
W James
WJ
Brown
Patrick O
PO
D018938:Caco-2 Cells; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation; D016764:Cell Polarity / Q000235:genetics*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051157:Frizzled Receptors / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006262:Health; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
D018797:Cell Cycle Proteins; D051157:Frizzled Receptors; D020033:Protein Isoforms; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin
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