The homeobox transcription factor Prox1 is highly conserved in embryonic hepatoblasts and in adult and transformed hepatocytes, but is absent from bile duct epithelium

Abstract

Prox1 is a transcription factor with two highly conserved domains, a homeobox and a prospero domain. It has been shown that Prox1 knock-out mice die during early embryonic stages and display a rudimentary liver. We have studied the expression of Prox1 at RNA and protein levels in chick, rat, mouse and human liver and in transformed and non-transformed hepatic cell lines. Prox1 is expressed in early embryonic hepatoblasts and is still expressed in adult hepatocytes. Prox1 protein is located in the nuclei of hepatoblasts, which grow into the neighboring embryonic mesenchyme. The expression pattern in chick, mouse, rat and human embryos is highly conserved. Besides albumin and alpha-fetal protein, Prox1 belongs to the earliest markers of the developing liver. In adult liver, Prox1 is expressed in hepatocytes but is absent from bile duct epithelial and non-parenchymal cells (Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells and myofibroblasts). Isolated primary hepatocytes and hepatoma cell lines (HepG2, Hep3B) are Prox1 positive, whereas the immortalized murine liver cell-line MMH, which constitutively expresses the receptor c-met, is Prox1 negative. Transfection of MMH with Prox1 cDNA increases the expression level significantly as compared to control transfectants. In HepG2 and Hep3B, the Prox1 levels are even up to 100 times higher. Our studies show that Prox1 is a highly conserved transcription factor, expressed in hepatocytes from the earliest stages of development into adulthood and over-expressed in hepatoma cell lines. Its absence from bile duct epithelial cells suggests a function for the specification of hepatoblasts into hepatocytes. The genes controlled by Prox1 need to be studied in the future.

Prox1 ablation in hepatic progenitors causes defective hepatocyte specification and increases biliary cell commitment

“…1F, arrows). This last finding is in contrast with a report showing Prox1 expression in hepatocytes, and absence of this protein in cholangiocytes, in the liver of adult rats (Dudas et al, 2004). It is probable that variability in the sensitivity of the immunodetection methods used in each study accounted for the discrepant results.…”

LYVE1 and PROX1 in the reconstruction of hepatic sinusoids after partial hepatectomy in mice

“…However, PROX1 is absent from hepatic sinusoids or venous endothelia due to the specification of progenitor cells [8]. In our present study, nuclear accumulation of PROX1 was detected in hepatocytes after partial hepatectomy.…”

The homeobox transcription factor Prox1 inhibits proliferation of hepatocellular carcinoma cells by inducing p53-dependent senescence-like phenotype

“…Livers from Prox1-null mice are much smaller than that of wild type mice because of reduced proliferation of hepatoblasts. 21,22 In addition, inactivation of Prox1 results in abnormal cellular proliferation, downregulation of the cell cycle inhibitors p27 and p57, and inappropriate apoptosis. 23 Therefore, Prox1 is an important regulator in the control of cell growth and may play a role in liver tumorigenesis.…”