Abstract
Epidermal growth factor (EGF) as well as prostaglandin F2 alpha (PGF2 alpha), when added to quiescent, confluent Swiss 3T3 cells, stimulate the initiation of DNA synthesis, which occurs with apparent first-order kinetics after a lag phase of 14-15 hr. These two growth factors appear to stimulate similar events; insulin enhances and hydrocortisone can inhibit the stimulatory effect of either. Here we show that the addition of EGF and PGF2 alpha together, however, results in a synergistic effect seen at the end of the lag phase, but only when EGF and PGF2 alpha are added within 6 hr of each other. Addition of one growth factor 10 or 15 hr after the other delayed the synergy for 15 hr after the addition of the second growth factor. Insulin further increased the rate of entry into the s phage stimulated by EGF and PGF2 alpha together, whereas hydrocortisone inhibited the stimulatory effect observed with either EGF or PGF2 alpha alone. These results suggest that, in spite of the common events responsible for the interactions with the two hormones, EGF and PGF2 alpha must have differences in their sequences of events that initiate DNA synthesis.
Full text
PDF![1004](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e0/319934/38289005f649/pnas00653-0368.png)
![1005](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e0/319934/e2c2229ae256/pnas00653-0369.png)
![1006](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e0/319934/74f8e3587333/pnas00653-0370.png)
![1007](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e0/319934/4b2930aaf794/pnas00653-0371.png)
![1008](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e0/319934/d3a0196b6763/pnas00653-0372.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brooks R. F., Bennett D. C., Smith J. A. Mammalian cell cycles need two random transitions. Cell. 1980 Feb;19(2):493–504. doi: 10.1016/0092-8674(80)90524-3. [DOI] [PubMed] [Google Scholar]
- Brooks R. F. Continuous protein synthesis is required to maintain the probability of entry into S phase. Cell. 1977 Sep;12(1):311–317. doi: 10.1016/0092-8674(77)90209-4. [DOI] [PubMed] [Google Scholar]
- Carpenter G., Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. doi: 10.1146/annurev.bi.48.070179.001205. [DOI] [PubMed] [Google Scholar]
- Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth. Nature. 1974 May 10;249(453):123–127. doi: 10.1038/249123a0. [DOI] [PubMed] [Google Scholar]
- Holley R. W. Control of growth of mammalian cells in cell culture. Nature. 1975 Dec 11;258(5535):487–490. doi: 10.1038/258487a0. [DOI] [PubMed] [Google Scholar]
- Jimenez de Asua L., O'Farrell M., Bennett D., Clingan D., Rugland P. Interaction of two hormones and their effect on observed rate of initiation of DNA synthesis in 3T3 cells. Nature. 1977 Jan 13;265(5590):151–153. doi: 10.1038/265151a0. [DOI] [PubMed] [Google Scholar]
- Mueller G. C. Biochemical events in the animal cell cycle. Fed Proc. 1969 Nov-Dec;28(6):1780–1789. [PubMed] [Google Scholar]
- Otto A. M., Zumbé A., Gibson L., Kubler A. M., Jimenez de Asua L. Cytoskeleton-disrupting drugs enhance effect of growth factors and hormones on initiation of DNA synthesis. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6435–6438. doi: 10.1073/pnas.76.12.6435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pardee A. B., Dubrow R., Hamlin J. L., Kletzien R. F. Animal cell cycle. Annu Rev Biochem. 1978;47:715–750. doi: 10.1146/annurev.bi.47.070178.003435. [DOI] [PubMed] [Google Scholar]
- Riddle V. G., Dubrow R., Pardee A. B. Changes in the synthesis of actin and other cell proteins after stimulation of serum-arrested cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1298–1302. doi: 10.1073/pnas.76.3.1298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudland P. S., Seifert W., Gospodarowicz D. Growth control in cultured mouse fibroblasts: induction of the pleiotypic and mitogenic responses by a purified growth factor. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2600–2604. doi: 10.1073/pnas.71.7.2600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith J. A., Martin L. Do cells cycle? Proc Natl Acad Sci U S A. 1973 Apr;70(4):1263–1267. doi: 10.1073/pnas.70.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TODARO G. J., GREEN H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963 May;17:299–313. doi: 10.1083/jcb.17.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Asua L. J., O'Farrell M. K., Clingan D., Rudland P. S. Temporal sequence of hormonal interactions during the prereplicative phase of quiescent cultured 3T3 fibroblasts. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3845–3849. doi: 10.1073/pnas.74.9.3845. [DOI] [PMC free article] [PubMed] [Google Scholar]