Plasma-protein production by rat hepatoma cells in culture, their variants and revertants.
A series of subclones of the H4II line of the Reuber H35 rat hepatoma produce substantial amounts of three plasma proteins, transferrin, alpha 1-antitrypsin and fibrinogen. Immunocytochemical staining demonstrated that each of these proteins is synthesized by essentially every cell of these cell populations. Cells of dedifferentiated variant clones either cease to produce the proteins, or exhibit a substantial reduction that is accompanied by variability in the synthetic activity of individual cells of the population. As previously observed with regard to angiotensinogen production, the variant clones clearly divide into two categories: those that show only a reduction in synthesis are able to give rise to revertants, whereas the negative clones fail to do so. Revertant cells exhibit a dramatic restoration of the synthesis of plasma proteins, which in some cases, exceeds by severalfold the rates seen in the differentiated clones of origin. In addition, the revertant cells synthesize alpha-fetoprotein, a function that is not expressed by H4II cells or its daughter subclones. Immunocytochemical staining revealed that, with regard to several plasma proteins including albumin, fibrinogen and alpha-fetoprotein, the cell populations of revertant clones are very heterogeneous, for only a fraction of the cells synthesizes each protein. Hybrid cells resulting from several types of crosses, exhibited extinction of the plasma proteins, the exception being transferrin, whose production was maintained, but at a reduced level and in only a fraction of the cells. Taken together, our results show that the expression of albumin and transferrin can be dissociated from one to another, and from that of fibrinogen, alpha 1-antitrypsin and angiotensinogen.
D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics; D014644:Genetic Variation; D006822:Hybrid Cells / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D014168:Transferrin / Q000096:biosynthesis / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis / Q000235:genetics
D001798:Blood Proteins; D014168:Transferrin; D000515:alpha 1-Antitrypsin; D005340:Fibrinogen