Negative regulation of mitogen-stimulated, anchorage-independent cell growth by a tumor-suppressor gene function.
Immortal, nontumorigenic cell lines of Syrian hamster embryo (SHE) cells with different tumor-suppressing activity were isolated. Subclones from the parental cells were isolated that either had retained (supB+) or lost (supB-) the ability to suppress tumorigenicity after hybridization with tumor cells. The growth properties of these cells were studied to determine how this tumor-suppressor gene function influences cell growth. When the cells were grown on plastic, their growth properties were similar, and neither cell type grew in soft agar containing 10% serum, which supported the growth of tumorigenic cells. However, in agar supplemented with growth factors and 10% serum, supB- cells formed colonies whereas supB+ cells did not. Efficient growth (colony-forming efficiencies greater than 20%) of supB- cells was obtained in agar supplemented with serum and a combination of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin (EPI) or with serum and basic fibroblast growth factor (bFGF). The effect of EPI and bFGF together was additive. supB+ cells failed to grow under any of these conditions, suggesting that the suppressor gene function blocked the growth response of the cells to multiple growth factors when the cells were suspended in agar. In SupB- cells, transforming growth factor-beta 1 and retinoic acid inhibited anchorage-independent growth response to EPI but not the growth response to bFGF. These observations are consistent with the hypothesis that bFGF stimulates the growth of supB- cells by a signal transduction pathway that differs from the pathway stimulated by EGF or PDGF. Thus, this suppressor gene function may regulate anchorage-independent growth at some common point in signal transduction for multiple mitogens.
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
C A
CA
Afshari
J C
JC
Barrett
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008647:Mesocricetus; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006133:Growth Substances; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D066246:ErbB Receptors; D011972:Receptor, Insulin; D017479:Receptors, Platelet-Derived Growth Factor