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The level of tyrosine kinase activity regulates the expression of p21/WAF1 in cancer cells.

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It is well documented that epidermal growth factor (EGF) inhibits proliferation of A431 and MDA-468 cells via activation of p21/WAF1. In the present study, we have shown that treatment of MDA-468 and A431 cells that express high levels of EGFR with 100 ng/ml of EGF leads to 14.9-fold increase in epidermal growth factor receptor (EGFR) autophosphorylation and high levels of p21/WAF1-induction (6. 7-fold), down regulation of cdk2 activity and growth arrest. When MDA-468 or A431 cells were simultaneously treated with 100 ng/ml EGF and RG13022, a relatively specific tyrosine kinase inhibitor, there was a significant reduction in p21/WAF1 levels. In contrast, when MDA-468, A432 cells that are treated with low levels of EGF (10 ng/ml) or other cells which express low to moderate levels of EGFRs such as MCF-7, MCF-10A, MDA-231 and SKBR-3 breast cells were exposed to 100 ng/ml of EGF there was a 3.8-fold increase in EGFR autophosphorylation, leading to 1.6-fold induction of p21/WAF1 and increased cell proliferation. These results suggest that the level of EGFR tyrosine kinase activity may regulate p21/WAF1 induction in cancer cells.
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Document Type: Research Article

Affiliations: Department of Pathology, Wayne State University, Detroit, MI 48201, USA.

Publication date: January 1, 1999

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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