Published Papers


Skip Navigation


UOU Logo

Top Menu

Total Search


Home > Research > Research Outcome >Published Papers

Document Contents

Published Papers

Search :

Search

Contribution of p53 in sensitivity to EGFR tyrosine kinase inhibitors in non-small cell lung cancer

Abstract
The emergence of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) with activating EGFR mutations is a major hindrance to treatment. We investigated the effects of p53 in primary sensitivity and acquired resistance to EGFR-TKIs in NSCLC cells. Changes in sensitivity to EGFR-TKIs were determined using p53 overexpression or knockdown in cells with activating EGFR mutations. We investigated EMT-related molecules, morphologic changes, and AXL induction to elucidate mechanisms of acquired resistance to EGFR-TKIs according to p53 status. Changes in p53 status affected primary sensitivity as well as acquired resistance to EGFR-TKIs according to cell type. Firstly, p53 silencing did not affect primary and acquired resistance to EGFR-TKIs in PC-9 cells, but it led to primary resistance to EGFR-TKIs through AXL induction in HCC827 cells. Secondly, p53 silencing in H1975 cells enhanced the sensitivity to osimertinib through the emergence of mesenchymal-to-epithelial transition, and the emergence of acquired resistance to osimertinib in p53 knockout cells was much slower than in H1975 cells. Furthermore, two cell lines (H1975 and H1975/p53KO) demonstrated the different mechanisms of acquired resistance to osimertinib. Lastly, the introduction of mutant p53-R273H induced the epithelial-to-mesenchymal transition and exerted resistance to EGFR-TKIs in cells with activating EGFR mutations. These findings indicate that p53 mutations can be associated with primary or acquired resistance to EGFR-TKIs. Thus, the status or mutations of p53 may be considered as routes to improving the therapeutic effects of EGFR-TKIs in NSCLC.

The administrative responsibility of the content.

By cliking the email below, you can send an e-mail to the person in charge.

Last Modified : Apr 9, 2013
  • Office : UOU International
  • Phone : +82-52-220-5957
  • Staff in Charge : Sean Park

Contents Review

Review the content back to the main content of the current page provides links to allow access.


Contact menu

CONNECT WITH UOU

Address

93 Daehak-ro, Nam-gu,
Ulsan (44610), Korea

Tel

Phone: +82-52-220-5952(~5959)

Fax

Fax: +82-52-224-2061

Email

QUICK LINK

Sitemap menu

CONTENTS

Join us and keep up-to-date on what is happenting around University of Ulsan.

Sitemap


Footer menu

CopyRight

Copyright 2012 University of Ulsan, All Rights Reserved.


Review Navigation