Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues

Mol Cell Biol. 1997 Mar;17(3):1626-41. doi: 10.1128/MCB.17.3.1626.


The hepatocyte nuclear factor 3alpha (HNF-3alpha) and 3beta proteins have homology in the winged helix/fork head DNA binding domain and regulate cell-specific transcription in hepatocytes and in respiratory and intestinal epithelia. In this study, we describe two novel isoforms of the winged helix transcription factor family, HNF-3/fork head homolog 11A (HFH-11A) and HFH-11B, isolated from the human colon carcinoma HT-29 cell line. We show that these isoforms arise via differential splicing and are expressed in a number of epithelial cell lines derived from tumors (HT-29, Caco-2, HepG2, HeLa, A549, and H441). We demonstrate that differentiation of Caco-2 cells toward the enterocyte lineage results in decreased HFH-11 expression and reciprocal increases in HNF-3alpha and HNF-3beta mRNA levels. In situ hybridization of 16 day postcoitus mouse embryos demonstrates that HFH-11 expression is found in the mesenchymal and epithelial cells of the liver, lung, intestine, renal cortex, and urinary tract. Although HFH-11 exhibits a wide cellular expression pattern in the embryo, its adult expression pattern is restricted to epithelial cells of Lieberkühn's crypts of the intestine, the spermatocytes and spermatids of the testis, and the thymus and colon. HFH-11 expression is absent in adult hepatocytes, but its expression is reactivated in proliferating hepatocytes at 4, 24, and 48 h after partial hepatectomy. Consistent with these findings, we demonstrate that HFH-11 mRNA levels are stimulated by intratracheal administration of keratinocyte growth factor in adult lung and its expression in an adult endothelial cell line is reactivated in response to oxidative stress. These experiments show that the HFH-11 transcription factor is expressed in embryonic mesenchymal and epithelial cells and its expression is reactivated in these adult cell types by proliferative signals or oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cloning, Molecular
  • DNA-Binding Proteins / genetics*
  • Epithelial Cells
  • Epithelium / metabolism
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors*
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental*
  • Growth Substances / pharmacology
  • Hepatocyte Nuclear Factor 3-alpha
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestines / embryology
  • Liver / cytology
  • Liver / metabolism
  • Liver Regeneration
  • Lung / embryology
  • Lung / metabolism
  • Male
  • Mesoderm / cytology
  • Mesoderm / metabolism*
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Organ Specificity
  • Oxidative Stress
  • Phosphoproteins / genetics
  • RNA, Messenger / analysis
  • Rats
  • Testis / metabolism
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • FGF7 protein, human
  • FOXA1 protein, human
  • FOXM1 protein, human
  • Fgf7 protein, mouse
  • Fgf7 protein, rat
  • Fibroblast Growth Factor 10
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Foxa1 protein, mouse
  • Foxa1 protein, rat
  • Foxm1 protein, mouse
  • Foxm1 protein, rat
  • Growth Substances
  • Hepatocyte Nuclear Factor 3-alpha
  • Nuclear Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Transcription Factors
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors

Associated data

  • GENBANK/U74612
  • GENBANK/U74613