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Loss of p53 induces epidermal growth factor receptor promoter activity in normal human keratinocytes

Oncogene volume 27, pages 4315–4323 (2008)Cite this article

Abstract

Overexpression of the epidermal growth factor receptor (EGFR) in human papillomavirus type 16-immortalized human keratinocytes (HKc) is caused by the viral oncoprotein E6, which targets p53 for degradation. We have previously observed that expression of p53 RNAi in normal HKc is associated with an increase in EGFR mRNA and protein. We now report that p53 RNAi induces EGFR promoter activity up to approximately 10-fold in normal HKc, and this effect does not require intact p53 binding sites on the EGFR promoter. Exogenous wild-type p53 inhibits the EGFR promoter at low levels, and activates it at higher concentrations. Yin Yang 1 (YY1), which negatively regulates p53, induces EGFR promoter activity, and this effect is augmented by p53 RNAi. Intact p53 binding sites on the EGFR promoter are not required for activation by YY1. In addition, Sp1 and YY1 synergistically induce the EGFR promoter in normal HKc, indicating that Sp1 may recruit YY1 as a co-activator. Wild-type p53 suppressed Sp1- and YY1-mediated induction of the EGFR promoter. We conclude that acute loss of p53 in normal HKc induces EGFR expression by a mechanism that involves YY1 and Sp1 and does not require p53 binding to the EGFR promoter.

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Acknowledgements

We thank Dr Omar Bagasra for discussion and advice in the construction and use of siRNA. This work was supported by grants from the National Institutes of Health: R01CA89502 and P20CA096427 to KEC, and EXPORT Center P20MD001770.

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  1. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, The South Carolina Cancer Center, Columbia, SC, USA

    A Bheda, K E Creek & L Pirisi

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  1. A Bheda
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  2. K E Creek
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  3. L Pirisi
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Correspondence to L Pirisi.

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Bheda, A., Creek, K. & Pirisi, L. Loss of p53 induces epidermal growth factor receptor promoter activity in normal human keratinocytes. Oncogene 27, 4315–4323 (2008). https://doi.org/10.1038/onc.2008.65

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