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ABSTRACT Overexpression of the _ERB_B-2 tyrosine kinase receptor, p185_ERB_B-2, is a common alteration in non-small cell lung cancer (NSCLC) and has been associated with poor prognosis and a
tumor drug resistance phenotype. In this study, we have examined the consequences of _ERB_B-2 depletion on DNA repair, cell cycle, and apoptosis using a panel of NSCLC cell lines
constitutively overexpressing _ERB_B-2 receptor. Depletion of the _ERB_B-2 was achieved using the tyrosine kinase inhibitor CP127,374 which promotes _ERB_B-2 degradation. Treatment with
CP127,374 concentrations which deplete _ERB_B-2 and inhibit tyrosine phosphorylation resulted in downregulation of DNA repair mechanisms and cell accumulation at G1 phase of the cell cycle.
G1 arrest was observed in cells with mutated p53 as well as cells lacking p53 protein, suggesting a p53-independent mechanisms. NSCLC cells which overexpress _ERB_B-2 were more resistant to
cisplatin-induced cytotoxicity in comparison to cells expressing low levels of _ERB_B-2. Treatment with CP127,374 alone did not result in any induction of apoptosis. A combination of
CP127,374 and cisplatin, however, was more potent in cell growth inhibition and induction of apoptosis compared to treatment with cisplatin alone. Together, our results further support a
pivotal role of _ERB_B-2 signaling in the regulatory balance between DNA repair, cell cycle checkpoints and apoptosis; all these mechanisms are essential determinants for tumor cell destiny
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FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ELEVATING CDCA3 LEVELS IN NON-SMALL CELL LUNG CANCER ENHANCES SENSITIVITY TO PLATINUM-BASED CHEMOTHERAPY Article Open
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TARGETED THERAPY IN EGFR-MUTATED LUNG ADENOCARCINOMA Article Open access 21 October 2021 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medicine and McGill Centre for
Translational Research in Cancer, Lady Davis Institute of the Sir Mortimer B Davis Jewish General Hospital, McGill University, Xiao-Li You, Lily Yen, Nie Zeng-Rong & Moulay A
Alaoui-Jamali * 3755 Cote Ste-Catherine, Montreal, H3T 1E2, Quebec, Canada Xiao-Li You, Lily Yen, Nie Zeng-Rong & Moulay A Alaoui-Jamali * Biotechnology Research Institute, National
Research Council, 6100 Royalmount Ave., Montreal, H4P 2R2, Quebec, Canada Ala-Eddin Al Moustafa Authors * Xiao-Li You View author publications You can also search for this author inPubMed
Google Scholar * Lily Yen View author publications You can also search for this author inPubMed Google Scholar * Nie Zeng-Rong View author publications You can also search for this author
inPubMed Google Scholar * Ala-Eddin Al Moustafa View author publications You can also search for this author inPubMed Google Scholar * Moulay A Alaoui-Jamali View author publications You can
also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE You, XL., Yen, L., Zeng-Rong, N. _et al._ Dual
effect of _ERB_B-2 depletion on the regulation of DNA repair and cell cycle mechanisms in non-small cell lung cancer cells. _Oncogene_ 17, 3177–3186 (1998).
https://doi.org/10.1038/sj.onc.1202246 Download citation * Received: 16 March 1998 * Revised: 24 June 1998 * Accepted: 25 June 1998 * Published: 17 December 1998 * Issue Date: 17 December
1998 * DOI: https://doi.org/10.1038/sj.onc.1202246 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link
is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * _erb_B-2 receptor * DNA repair * cell cycle *
apoptosis