Pioglitazone attenuates the inhibitory effect of phorbol ester on epidermal growth factor receptor autophosphorylation and tyrosine kinase activity.

A new anti-diabetic drug, pioglitazone, was tested as to whether it could ameliorate the decreased kinase activity of epidermal growth factor (EGF) receptor induced by phorbol ester (PMA) in A431 cells. The treatment of A431 cells with PMA decreased the tyrosine kinase activity of EGF receptors to 37% of normal in autophosphorylation and to 24% in tyrosine kinase activity toward Glu/Tyre synthetic polymers. Co-incubation of the cells with pioglitazone and PMA improved the receptor tyrosine kinase activity to 81% of control. Pioglitazone treatment alone did not change the kinase activity of EGF receptors. Pioglitazone did not decrease the PMA-activated protein kinase C activity and did not affect the protein tyrosine phosphatases activity in A431 cells. These results suggest that pioglitazone may act as a specific antagonist to the inhibitory effect by protein kinase C on the EGF receptor tyrosine kinase.