Formes moléculaires fœtales d'enzymes dans l'hépatome

Abstract

Summary The resurgence of fetal type aldolases in hepatoma offers a striking example of the fetal pattern of enzymes in some cancerous tissues. In slow growing hepatomas (transplantable or induced by 3'MeDAB) we have observed an increase of aldolase A (muscle type) which is relatively abundant in fetal liver but present only in small amounts in normal adult liver. This increase is proved by the elevation of the aldolase activity ratio, by the action of specific antiserum, and by electrophoresis. Electrophoresis on starch gel shows that aldolase A is hybridized with the normal liver type aldolase (aldolase B). This hybridization indicates a synthesis of the two aldolases by the same type of cells. In fast-growing hepatomas (ascitic or solid) aldolase B is absent or nearly absent ; aldolase A is present in large amounts. Moreover, the presence of a third type of aldolase, aldolase C (brain type), which is completely absent from normal adult rat liver, has been demonstrated in fetal and in cancerous liver. This was proved by (a) the aldolase activity ratio (about 30.0 instead of 1.0), (b) electrophoresis which shows in fetal liver and in hepatoma anodic isozymes similar to brain aldolase isozymes ; (c) the action of specific antiserum anti aldolase C. The degree of inhibition by each specific antiserum corresponds roughly to that expected from the electrophoretic pattern. Fetal liver contains the three types A, B and C ; fast-growing hepatomas contain aldolases A and C and very little aldolase B. Aldolase C from fast-growing hepatomas was partly purified. Similar observations were made in human primary liver cancer. A fetal liver pattern has also been found for some other enzymes in hepatomas by several authors ; mainly hexokinases, lactic dehydrogenases, glutaminases and branched chain amino acid transaminases ; it can be compared with the resurgence of fetal antigens in cancer tissues and sera. And although the placental type of alkaline phosphatase found in cancer by Fishman was not found in fetus, it is noteworthy that placenta is an embryonic tissue. S. Weinhouse has shown that the liver-type isozyme of several enzymes is replaced by non-hepatic types in fast-growing hepatomas. This « fetal patternis not specific for carcinogenesis : for example « fetal-typeof several muscle enzymes is present in atrophied and dystrophic muscle. In conclusion, it seems likely that in several pathological states the biosynthesis of the adult form of enzymes is preferentially « repressedwhile the fetal, or less differentiated molecular form would be derepressed.