Downregulation of hepatocyte nuclear factor-4alpha and its role in regulation of gene expression by TGF-beta in mammary epithelial cells

Experimental Cell Research
Fumihiro IshikawaMotoko Shibanuma

Abstract

We found that a specific isoform of hepatocyte nuclear factor 4alpha (HNF-4alpha), HNF-4alpha8, was expressed in mouse mammary epithelial NMuMG cells, and that its expression was repressed by TGF-beta. The repression was interfered by dominant negative forms of activin receptor-like kinase 5 (ALK5) and Smad3, and sensitive to cycloheximide, suggesting the involvement of additional protein(s) as well as ALK5 and Smad3 in the repression. Further study showed that high mobility group A2 (HMGA2), which is reported to be directly upregulated by Smads, repressed HNF-4alpha8 expression. Therefore, it is likely that HMGA2 mediates the downregulation of HNF-4alpha8 downstream of ALK5 and Smads To determine the significance of the downregulation of HNF-4alpha8 in TGF-beta signaling, we performed DNA microarray analysis and extracted a subgroup of TGF-beta1-regulated genes, including tenascin C and tissue inhibitor of metalloproteinase 3 (TIMP-3), whose regulation by TGF-beta1 was attenuated by forced expression of HNF-4alpha8. HMGA2 has recently emerged as a transcriptional organizer of TGF-beta signaling, regulating several key factors involved in epithelial-mesenchymal transition (EMT). In this study, we identified an isoform of HNF-4a...Continue Reading

References

Oct 27, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B WangK P Ponder
Mar 24, 2004·Critical Reviews in Oncology/hematology·Elise LambertEmmanuelle Petitfrère
Aug 16, 2005·Current Opinion in Cell Biology·Margit A HuberHartmut Beug
Aug 27, 2005·Oncogene·Jiri Zavadil, Erwin P Böttinger
Jul 13, 2006·The Journal of Cell Biology·Sylvie ThuaultAristidis Moustakas
Aug 15, 2006·Biochimica Et Biophysica Acta·Katerina Pardali, Aristidis Moustakas
Sep 5, 2006·Cancer Metastasis Reviews·Sonia B Jakowlew

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Citations

Oct 20, 2009·Journal of Cell Communication and Signaling·Kim S Midwood, Gertraud Orend
Aug 19, 2010·Journal of Cellular Physiology·A FeuerbornH-J Gröne

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