Contributions of the Epidermal Growth Factor Receptor to Acquisition of Platinum Resistance in Ovarian Cancer Cells

PloS One
Michaela L GranadosSabrina L Samudio-Ruiz

Abstract

Acquisition of platinum resistance following first line platinum/taxane therapy is commonly observed in ovarian cancer patients and prevents clinical effectiveness. There are few options to prevent platinum resistance; however, demethylating agents have been shown to resensitize patients to platinum therapy thereby demonstrating that DNA methylation is a critical contributor to the development of platinum resistance. We previously reported the Epidermal Growth Factor Receptor (EGFR) is a novel regulator of DNA methyltransferase (DNMT) activity and DNA methylation. Others have shown that EGFR activation is linked to cisplatin treatment and platinum resistance. We hypothesized that cisplatin induced activation of the EGFR mediates changes in DNA methylation associated with the development of platinum resistance. To investigate this, we evaluated EGFR signaling and DNMT activity after acute cisplatin exposure. We also developed an in vitro model of platinum resistance to examine the effects of EGFR inhibition on acquisition of cisplatin resistance. Acute cisplatin treatment activates the EGFR and downstream signaling pathways, and induces an EGFR mediated increase in DNMT activity. Cisplatin resistant cells also showed increased D...Continue Reading

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Citations

Jun 9, 2016·Expert Review of Molecular Diagnostics·Marta SzajnikTheresa L Whiteside
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Jul 15, 2020·Iranian Biomedical Journal·Arash PoursheikhaniGhaffari Seyed H
Jul 13, 2018·Journal of Experimental & Clinical Cancer Research : CR·Katia ReaAntonella Tomassetti

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Methods Mentioned

BETA
protein assay
Assay

Software Mentioned

GraphPad Prism
SoftMax Pro

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