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PMID: 3295869 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

Brown KD, Holley RW

Abstract

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. 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 we 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.

MeSH Terms
Animals Bombesin/pharmacology Cell Line Cells, Cultured DNA Replication/drug effects Drug Synergism Growth Inhibitors/isolation & purification,pharmacology Growth Substances/pharmacology Insulin/pharmacology Kinetics Mice Peptides/pharmacology Platelet-Derived Growth Factor/pharmacology Transforming Growth Factors Vasopressins/pharmacology
Chemicals
Growth Inhibitors Growth Substances Insulin Peptides Platelet-Derived Growth Factor Vasopressins Transforming Growth Factors Bombesin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Brown K D
Holley R W
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52 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1987-06-00
Pages
3743-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC304952
Subset
IM
Grants
NCI NIH HHS · CA11176 · United States
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