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Negative regulation of mitogen‐stimulated, anchorage‐independent cell growth by a tumor‐suppressor gene function
Author(s) -
Afshari Cynthia A.,
Barrett J. Carl
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940070407
Subject(s) - biology , growth factor , epidermal growth factor , basic fibroblast growth factor , platelet derived growth factor receptor , cell growth , fibroblast growth factor , cell culture , microbiology and biotechnology , retinoic acid , platelet derived growth factor , endocrinology , medicine , biochemistry , receptor , genetics
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‐β1 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.