Protein tyrosine kinase blockers of the tyrphostin family inhibited the EGF-dependent proliferation of human and guinea pig keratinocytes grown in culture and induced their growth arrest. These blockers also significantly inhibited the growth of epidermal keratinocytes, but not of dermal cells, in whole skin organ culture from both guinea pig and human origin. The antiproliferative activity of these tyrphostins correlated quantitatively with their potency as inhibitors of EGF receptor autophosphorylation and the EGF-dependent protein phosphorylation of intracellular target proteins in the keratinocyte. Furthermore, no significant cell cytotoxicity or reduction in serine and threonine phosphorylation of many intracellular polypeptides were observed upon incubation of the cells with tyrphostins like AG213. The complete growth arrest induced by the tyrphostins is fully reversible and upon their removal the keratinocytes resumed their growth with the original growth rate. Because of the nontoxic nature of these compounds and their growth-arresting properties, we suggest their use as agents to treat hyperproliferative conditions of human skin.
The inhibition of EGF-dependent proliferation of keratinocytes by tyrphostin tyrosine kinase blockers.
- Views Icon Views
- PDF LinkPDF
- Share Icon Share
- Search Site
A Dvir, Y Milner, O Chomsky, C Gilon, A Gazit, A Levitzki; The inhibition of EGF-dependent proliferation of keratinocytes by tyrphostin tyrosine kinase blockers.. J Cell Biol 15 May 1991; 113 (4): 857–865. doi: https://doi.org/10.1083/jcb.113.4.857
Download citation file: