Cytoskeletal and morphological changes associated with the specific suppression of the epidermal growth factor receptor tyrosine kinase activity in A431 human epidermoid carcinoma

Experimental Cell Research
J M Nelson, D W Fry

Abstract

The epidermal growth factor (EGF) receptor is well known as a mediator of mitogenic signaling and its tyrosine kinase activity has been suggested as a viable target in cancer chemotherapy. To explore the consequences of abolishing the kinase activity of this receptor, we have utilized a potent and specific inhibitor of the enzyme, PD 153035, to sustain a long-term suppression of its activity. This compound inhibits EGF receptor autophosphorylation in cells with an IC50 in the low nanomolar range and does not block PDGF or FGF receptor kinase until concentrations are greater than 10 microM. [1] Human epidermoid carcinoma A431 cells were grown in the presence of PD 153035 and were passed weekly until cells grew in the presence of 1 microM inhibitor. These cells, referred to as A431R, showed a remarkable change in morphology, becoming flattened and spread out. A comparison of the sensitivity of EGF receptor autophosphorylation to PD 153035 between A431 and A431R showed a similar dose response, indicating that the cells had not developed any defect in the kinase which might make it resistant to the inhibitor. Likewise, EGF receptor autophosphorylation in response to exogenously added EGF, as well as receptor internalization, was si...Continue Reading

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Citations

Mar 31, 2015·Journal of Pharmacokinetics and Pharmacodynamics·Stephan BenayThierry Lave
Aug 10, 2006·The Journal of Biological Chemistry·Hiroaki KonishiHisaaki Taniguchi
May 9, 2000·Biochemical Pharmacology·G CassinelliF Zunino
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