Showing papers by "Michael B. Sporn published in 1982"

Synergistic interaction of two classes of transforming growth factors from murine sarcoma cells.

Abstract: Transforming growth factors (TGFs) isolated from murine sarcoma virus-transformed 3T3 cells have been separated by high-pressure liquid chromatography into two subsets. One subset, called TGFα, competes with epidermal growth factor (EGF) for receptor sites, whereas the other, called TGFβ, does not. TGBβ, purified by high-pressure liquid chromatography, will not induce formation of large colonies of cells in soft agar in the absence of TGFα or EGF. However, the combined action of either TGFα or EGF (which by themselves are relatively ineffective in promoting growth of cells in soft agar) together with TGFβ results in a potent synergistic effect, with formation of large colonies. Chemically modified analogs of EGF also potentiate TGFβ activity to the extent that they bind to the EGF receptor. It is suggested that TGFβ may be an important mediator of the known effects of both TGFα and EGF on neoplastic transformation.

Isolation from murine sarcoma cells of novel transforming growth factors potentiated by EGF

Abstract: Polypeptides classified as transforming growth factors (TGFs) have been found in various neoplastic cells and tumour tissues1–5, and most recently in many non-neoplastic tissues6. These TGFs are low-molecular-weight (7,000–20,000) acid-stable polypeptides, which induce anchorage-dependent non-neoplastic indicator cells to form progressively growing colonies in soft agar. Certain extracellular TGFs isolated from conditioned medium derived from both rodent sarcoma virus-transformed cells and several human tumour cell lines have been shown to compete with epidermal growth factor (EGF) for membrane receptors1,3,4,7. By direct extraction from Moloney sarcoma virus (MSV)-transformed cells, we have isolated two distinct classes of intracellular TGFs, one of which competes with EGF for receptor binding sites, whereas the other does not. We report here that after purification by HPLC, the colony-forming activity of the TGFs that do not compete with EGF for receptor binding was enhanced 100-fold by the addition of EGF. This ability to enhance the growth-stimulating effects of the TGFs is specific to EGF, as insulin, the insulin-like growth factors, platelet-derived growth factor and nerve growth factor do not show this property. In contrast, the colony-forming activity of TGFs that compete with EGF for receptor binding is not potentiated by EGF.

Influence of 15 retinoic acid amides on urinary bladder carcinogenesis in the mouse.

Abstract: A series of experiments was conducted to determine the efficacy of 15 synthetic retinoic acid amides (retinamides) as inhibitors of chemical carcinogenesis of the urinary bladder in C57BL/6 x DBA/2F1 mice. Eight of the retinamides tested had significant protective activity when administered at nontoxic levels in the diet. Minor structural alterations, such as the addition of a methyl or hydroxyl group to the terminal amide moiety had a major influence on the anticarcinogenic activity of the retinamides. Although 13-cis retinamides generally were less toxic on a molar basis than were their all-trans isomers, no consistent pattern of differential anticarcinogenic activity was noted among the six pairs of all-trans and 13-cis isomers tested. All-trans-4-hydroxyphenyl retinamide was among the most active and least toxic of the retinoids tested, and appears to be the compound of choice for further study.