Interactions between the epidermal growth factor receptor and typeⅠ protein kinase A in therapy of malignant tumor / 中国癌症杂志

ABSTRACT

The overexpression of EGFR and the typeⅠcAMPdependent protein kinase(PKAⅠ) has been found in most cancer tissue and tumour cells.The blockade of EGFR activation by using anti-EGFR monoclonal antibodies(MAbs) and inhibition of PKAⅠ expression by specific pharmacological agents such as the selective cAMP analogue 8-Cl-cAMP has been proposed as a potential anticancer therapy.We have shown that an interaction between EGFR and PKAⅠ occurs through direct binding of the RⅠsubunit to the Grb2 adaptor protein.We have demonstrated that the functional interaction between the EGFR and the PKAⅠ pathways could have potential therapeutic implications.In fact,the combined interference with both EGFR and PKAⅠ with specific pharmacological agents,has a cooperative antiproliferative effect on human cancer cell lines in vitro and in vivo.Studies on the antitumor activity of this combination are under human clinical trial evaluation.