[Reciprocal regulation of growth and differentiation in hepatocytes by cell surface modulator and loss of regulation during carcinogenesis].
In primary monolayer cultures of mature rat hepatocytes, cell growth and hepatocyte-specific functions were mediated by a cell surface component (named the cell surface modulator) via cell-cell contact. The modulator activity was heat-labile and trypsin-sensitive. Activity was also found in plasma membranes from kidney, brain, lung, and erythrocytes. The modulator was solubilized by 4% octylglucoside plus 4M guanidine HCl from liver membranes. The molecular weight of the modulator was 670KD determined by Sephacryl S-400 gel filtration. Hepatoma cells established from Reuber and Morris hepatoma did not show any cell density-dependency on either cell growth or hepatocyte-specific function. However, these hepatoma cells had strong cell surface modulator activity. These results suggest that hepatoma cells have lost their cell density-dependent regulation because they have lost the ability to respond to the cell surface modulator. Characterization of the cell surface modulator and its mechanism of transmitting a signal for gene regulation would be helpful in understanding the process by which cells assemble into tissues in vivo and the mechanism of changes in gene expression in tissue during development, regeneration and carcinogenesis.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000502:physiology; D008099:Liver / Q000166:cytology*; D008113:Liver Neoplasms / Q000473:pathology*; D008565:Membrane Proteins / Q000502:physiology*; D051381:Rats; D014357:Trypsin / Q000494:pharmacology
D000596:Amino Acids; D006133:Growth Substances; D008565:Membrane Proteins; D004247:DNA; D014357:Trypsin