Insulin-like synergistic stimulation of DNA synthesis in Swiss 3T3 cells by the BSC-1 cell-derived growth inhibitor related to transforming growth factor type. beta
A cell growth inhibitor (GI), purified from BSC-1 cell-conditioned medium, has little if any effect on DNA synthesis when added alone to monolayer cultures of quiescent Swiss mouse 3T3 cells in serum-free medium. However, the inhibitor, which is closely related to transforming growth factor type ..beta.. (TGF-..beta..), exhibits a pronounced synergistic stimulation of DNA synthesis in combination with certain peptide (bombesin, vasopressin) or polypeptide (platelet-derived growth factor) mitogens. /sup 125/I-EGF binding was measured and the efflux of /sup 45/Ca/sup 2 +/ was measured in response to mitogen stimulation. A similar synergistic response has been demonstrated for TGF-..beta.. purified from human platelets. In the presence of 3 nM bombesin, a half-maximal stimulation of DNA synthesis was obtained at a GI concentration of approximately 60 pg/ml, with a maximal response at approximately 600 pg/ml. The synergistic interactions demonstrated by GI or TGF-..beta.. in stimulating Swiss 3T3 cells closely resemble those previously shown for insulin, and the authors have observed that GI does not synergize with insulin to stimulate DNA synthesis in these cells. Like insulin, and in contrast to bombesin, vasopressin, and platelet-derived growth factor, GI does not activate cellular inositolphospholipid hydrolysis, calcium mobilization, or cross-regulation of epidermal growth factor receptor affinity. These results raise the possibility that the biochemical pathways activated by GI/TGF-..beta.. and insulin converge at a post-receptor stage.
- Research Organization:
- Agricultural and Food Research Council Institute of Animal Physiology, Cambridge, England
- OSTI ID:
- 5301175
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:12
- Country of Publication:
- United States
- Language:
- English
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FIBROBLASTS
DNA REPLICATION
GROWTH FACTORS
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MICE
PEPTIDES
SYNERGISM
THYMIDINE
TRITIUM COMPOUNDS
VASOPRESSIN
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CALCIUM ISOTOPES
CONNECTIVE TISSUE CELLS
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ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MITOGENS
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES
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550201 - Biochemistry- Tracer Techniques