The insulin like growth factors I and II are the most ubiquitous in the mammalian embryo. Moreover they play a pivotal role in the development and growth of tumours. The bioavailability of these growth factors is regulated on a transcriptional as well as on a posttranslational level. The expression of non-signalling receptors as well as binding proteins does further tune the local concentration of IGFs. This paper aims at reviewing how the transcription of the IGF genes is regulated. The biological significance of these control mechanisms will be discussed.

Apoptosis is nowadays recognized as an important mechanism by which cells can be eliminated from the organism. In particular its role in tissue modelling during embryogenesis has been highlighted. The human teratoma cell line Tera 2, which in several respects acts as a human embryonic stem cell, can be induced to undergo apoptosis by reducing the serum content of the tissue culture medium. We report here that this process can be reversed by replacing serum with the heparin-binding growth factors, acidic FGF and basic FGF. In contrast, neither of the mammalian transforming growth factors (TGF-beta 1-3) managed to exert any effect on growth or apoptosis in Tera 2 cells.

Rcccivcd R Januury 1991The human teratocarcinoma ccl1 line Tcra 2 can bc induced IO di.qcrcJrtiatc in vitro after exposure to rctinoic acid. We show in this pq%r thtrt whereas the K-FGF oncogcnc is cxprrsscd in undiffcrcnti;ited cells, addition of retinoic acid rapidly (~60 min) downrcgulutcs the expression of this pcnc. However, when cells are cultured in AA for an extended pcricsd of timr (> I5 days) KSFGF transcripts rcilppcar. WC also report that K-FGF is expressed in approximately one-third of primary humen gclm cell tumours but no\ in the corrcspondiny normal tcsticuhir tissue. K-FGF; Teralocarcinoma INTRODUCTIONThe heparin binding growth factor family now comprises a number of structurally related polypeptides which influence many aspects of cellular physiology, differentiation and proliferation. The acidic and basic fibroblast growth factors, originally isolated from pituitary and central nervous system respectively, are potent mitogens, both in vitro and in vivo [l] and since their discovery have been shown to stimulate proliferation of a wide variety of cells in tissue and organ culture [2,3]. The FGFs are also interesting in the light of their diveree deve!opmental effects. Synthesis of heparin binding growth factors occurs both in perimplantation stages of mammalian embryogenesis and later during orgsonogenesis. In both these situations there is circumstantial evidence for a pleiotropic response of target cells to the factor: different concentrations of the factor leading to proliferation, cell migration and differentiation f4,5]. Not only are these processes important in morphogenesis but also in the metastasis and angiogenic properties of turnours, and there is strong evidence that FGF or related molecules are potent stimulators of the capillary endothelial cell response to tumours 131.Within recent years the FGF family has expanded to include proteins encoded by at least 7 different genes. In addition, genes encoding FGF-receptors have been recently characterized. Genes encoding the FGF homologues K-FGF?hst, int-2 and FGF-5 were originally isolated as oncogenes by DNA tsansfection assay, Correspondence addrem: W. EngstMm,

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