Abstract
In order to determine the biological effects of activation of the c-fos protooncogene on growth and differentiation of BALB/MK mouse keratinocytes, these cells were transfected with the plasmid pMAN-fos, which encompasses the human c-fos coding region under transcriptional control of a mouse mammary tumor virus promoter, as well as the gene encoding neomycin phosphotransferase. Of approximately 70 individual clones obtained by selection in Geneticin, 5 clones that constitutively expressed c-fos mRNA as well as p55fos protein were selected for phenotypic analysis. Each of these clones displayed density-dependent growth arrest at confluency when deprived of serum and mitogens. DNA synthesis could be reinitiated in quiescent cultures by treatment with epidermal growth factor to a similar extent as in the parental line. In four of five fos transfectants, insulin-like growth factor 1 potentiated the mitogenic response to epidermal growth factor more than 10-fold, compared to only 2.5-fold in the parental cells. The enhanced response to insulin-like growth 1 could not be attributed to changes in the number or the affinity of receptors for the growth factor. Finally, the constitutive expression of c-fos did not interfere with the induction of terminal differentiation by calcium.
Footnotes
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↵1 This work was supported in part by USPHS Grant CA-41556 from the National Cancer Institute.
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↵2 To whom requests for reprints should be addressed.
- Received September 27, 1989.
- Accepted July 19, 1990.
- ©1990 American Association for Cancer Research.
Volume 50, Issue 20
