CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Faaland, C. A.
Right arrow Articles by Thomas, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Faaland, C. A.
Right arrow Articles by Thomas, T. J.

Cell Growth & Differentiation, Vol 6, Issue 2 115-121, Copyright © 1995 by American Association of Cancer Research


ARTICLES

Inhibition of epidermal growth factor-stimulated EGF receptor tyrosine kinase activity in A431 human epidermoid carcinoma cells by polyamines

CA Faaland, JD Laskin and TJ Thomas
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903, USA.

Polyamines--putrescine, spermidine, and spermine--are ubiquitous cellular components that play an important role in cell growth and differentiation. Using A431 cells, a cell line that overexpresses the epidermal growth factor (EGF) receptor, we found that polyamines modulate EGF-mediated growth inhibition. The natural polyamine, putrescine, was the most effective, followed by diamines containing lower and higher methylene bridging between the amino groups. To understand the mechanism, we examined the effects of polyamines on EGF-mediated signal transduction in A431 cells. All three polyamines partially inhibited EGF-receptor tyrosine kinase activity in a dose-dependent manner. The maximal inhibition was 75% with spermidine. Polyamine effects were exerted 12-16 h after treatment, although HPLC analysis revealed uptake of polyamines within 1 h. Homologues of putrescine had no significant effect on tyrosine kinase activity, indicating structural specificity of naturally occurring polyamines in this process. Amine oxidase inhibitors did not alter spermidine and spermine-mediated effects, suggesting that the inhibition of tyrosine kinase activity was not a consequence of the oxidative metabolism of polyamines. Difluoromethylornithine, a specific inhibitor of polyamine biosynthesis, did not affect EGF receptor tyrosine kinase activity. Polyamines also had no effect on EGF receptor levels or EGF-EGF receptor high-affinity binding, indicating that they are not competitive inhibitors of the EGF receptor tyrosine kinase. Our results suggest that polyamine action in A431 cells involves modulation of EGF receptor signal transduction pathways.





HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1995 by the American Association of Cancer Research.