ROLE OF INTRACELLULAR COMMUNICATIONS IN H EPATOCYTE DIFFERENTIATION AND ALTERATIONS DURING CARCINOGENESIS

The liver epoch like other tissue epochs occurs after that different e vents have induced heterogeneity in embryonic cells which results in d istinct evolutionnary processes. These events and those of organogenes is like << induction >> are deeply dependent on cell-cell communicatio ns. Cell-cell interactions involve either soluble factors (hormones, g rowth factors), extracellular matrix or plasma membrane proteins respo nsible for cell-cell recognition and/or adhesion. All these plasma mem brane signals are transduced to the nucleus and modulate the expressio n of groups of genes. To be functionnally stable along the adult stage the liver has to maintain an ordered activity of cell renewal. This b alance between proliferation and differentiation is, at least in part, controlled by cell-cell communications. Therefore, it is not surprisi ng that intercellular communications are altered during hepatocarcinog enesis. They involve changes in the distribution of junctions, in the amounts of extracellular matrix components and/or growth factors which all result in modifying the differentiation/proliferation balance. Ce ll culture models have been used for these different studies; new in v itro systems should be set up in the near future by taking advantage o f the targeted hepatocarcinogenesis in transgenic mouse.