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PMID: 8196606 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Effect of a null mutation of the insulin-like growth factor I receptor gene on growth and transformation of mouse embryo fibroblasts.

Molecular and cellular biology ·Vol. 14 ·No. 6 ·1994-06-00 ·Pages 3604-12

Sell C, Dumenil G, Deveaud C, Miura M, Coppola D, DeAngelis T, Rubin R, Efstratiadis A, Baserga R

Abstract

Fibroblast cell lines, designated R- and W cells, were generated, respectively, from mouse embryos homozygous for a targeted disruption of the Igf1r gene, encoding the type 1 insulin-like growth factor receptor, and from their wild-type littermates. W cells grow normally in serum-free medium supplemented with various combinations of purified growth factors, while pre- and postcrisis R- cells cannot grow, as they are arrested before entering the S phase. R- cells are able to grow in 10% serum, albeit more slowly than W cells, and with all phases of the cell cycle being elongated. An activated Ha-ras expressed from a stably transfected plasmid is unable to overcome the inability of R- cells to grow in serum-free medium supplemented with purified clones. Nevertheless, even in the presence of serum, R- cells stably transfected with Ha-ras, alone or in combination with simian virus 40 large T antigen, fail to form colonies in soft agar. Reintroduction into R- cells (or their derivatives) of a plasmid expressing the human insulin-like growth factor I receptor RNA and protein restores their ability to grow with purified growth factors or in soft agar. The signaling pathways participating in cell growth and transformation are discussed on the basis of these results.

Related Genes
c-Ha-ras ras
MeSH Terms
Animals Cell Cycle/drug effects Cell Division/drug effects,physiology Cell Line, Transformed Cell Transformation, Neoplastic Cells, Cultured Embryo, Mammalian Epidermal Growth Factor/pharmacology Genes, ras Growth Substances/pharmacology Insulin/pharmacology Insulin-Like Growth Factor I/pharmacology Kinetics Mice Mutation Phenotype Platelet-Derived Growth Factor/pharmacology Receptor, IGF Type 1/biosynthesis,genetics Signal Transduction Transfection
Chemicals
Growth Substances Insulin Platelet-Derived Growth Factor Epidermal Growth Factor Insulin-Like Growth Factor I Receptor, IGF Type 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sell C
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Dumenil G
Deveaud C
Miura M
Coppola D
DeAngelis T
Rubin R
Efstratiadis A
Baserga R
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.6.3604-3612.1994
Published
1994-06-00
Pages
3604-12
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358728
Subset
IM
Grants
NCI NIH HHS · CA 56309 · United States
NIGMS NIH HHS · GM 33694 · United States
NICHD NIH HHS · HD 28342 · United States
External Links
PubMed source DOI: 10.1128/mcb.14.6.3604-3612.1994 PMC Full Text View journal details
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