Letter | Published:

Epidermal growth factor, like phorbol esters, induces plasminogen activator in HeLa cells

Nature volume 274, pages 696697 (17 August 1978) | Download Citation

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Abstract

STUDIES on the action of the tumour-promoting compound 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and related plant diterpenes, in cell culture systems have revealed several unusual biological properties1–3. These include the induction of plasminogen activator production2 as well as several other phenotypic changes resembling those seen in cells transformed by chemical carcinogens or viruses1. Furthermore, these compounds are extremely potent inhibitors of several types of terminal differentiation1,4,5, all these effects being exerted by very low concentrations of the active compounds, in the range of 10−9M. In addition, the activities of a series of such compounds, with respect to their cell culture effects, in general parallel their activities as promoters in the mouse skin two-stage carcinogenesis system1,6. We have previously postulated that the highly pleiotropic effects of these compounds may be due to their ability to usurp the effector system of an endogenous growth regulatory hormone1,3,7,8. The polypeptide hormone epidermal growth factor (EOF) is a possible candidate for this putative substance as it shares several biological properties with the phorbol esters9–14. Consistent with this hypothesis are recent results from our laboratory indicating that TPA is a potent inhibitor of the binding of 125I-EGF to its cellular receptors3. We report here that EGF and TPA resemble each other in their ability to serve as potent inducers of plasminogen activator production in HeLa cell cultures. Our results further suggest that the mechanism of EGF induction ot this protease is also similar to that of induction produced by TPA and related tumour promoters.

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Author information

Affiliations

  1. Institute of Cancer Research and Division of Environmental Sciences, Columbia University College of Physicians and Surgeons, 701 West 168th Street, New York, New York 10032

    • LIH-SYNG LEE
    •  & I. BERNARD WEINSTEIN

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DOI

https://doi.org/10.1038/274696a0

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