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Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
BACKGROUND: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. METHODS: We evaluated whether SCLC transformation or neuroendocrine (NE) differe...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Korean Academy of Tuberculosis and Respiratory Diseases
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790027/ https://www.ncbi.nlm.nih.gov/pubmed/24101933 http://dx.doi.org/10.4046/trd.2013.75.3.95 |
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author | Chang, Youjin Kim, Seon Ye Choi, Yun Jung So, Kwang Sup Rho, Jin Kyung Kim, Woo Sung Lee, Jae Cheol Chung, Jin-Haeng Choi, Chang-Min |
author_facet | Chang, Youjin Kim, Seon Ye Choi, Yun Jung So, Kwang Sup Rho, Jin Kyung Kim, Woo Sung Lee, Jae Cheol Chung, Jin-Haeng Choi, Chang-Min |
author_sort | Chang, Youjin |
collection | PubMed |
description | BACKGROUND: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. METHODS: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. RESULTS: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. CONCLUSION: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity. |
format | Online Article Text |
id | pubmed-3790027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Korean Academy of Tuberculosis and Respiratory Diseases |
record_format | MEDLINE/PubMed |
spelling | pubmed-37900272013-10-07 Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Chang, Youjin Kim, Seon Ye Choi, Yun Jung So, Kwang Sup Rho, Jin Kyung Kim, Woo Sung Lee, Jae Cheol Chung, Jin-Haeng Choi, Chang-Min Tuberc Respir Dis (Seoul) Original Article BACKGROUND: Small cell lung cancer (SCLC) transformation during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has been suggested as one of possible resistance mechanisms. METHODS: We evaluated whether SCLC transformation or neuroendocrine (NE) differentiation can be found in the cell line model. In addition, we also investigated its effect on responses to conventional chemotherapeutic drugs of the SCLC treatment. RESULTS: Resistant cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785 and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were established. Among them, two resistant cell lines, A549/GR (resistant to gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were found only in A549/GR in western blotting, suggesting that NE differentiation occurred in A549/GR. A549/GR cells were more sensitive to etoposide and cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549 cells, which also made them more sensitive to etoposide and cisplatin than parental cells. Furthermore, we found a tissue sample from a patient which showed increased expressions of CD56 and synaptophysin after development of resistance to erlotinib. CONCLUSION: NE differentiation can occur during acquisition of resistance to EGFR-TKI, leading to increased chemosensitivity. The Korean Academy of Tuberculosis and Respiratory Diseases 2013-09 2013-09-30 /pmc/articles/PMC3790027/ /pubmed/24101933 http://dx.doi.org/10.4046/trd.2013.75.3.95 Text en Copyright©2013. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. http://creativecommons.org/licenses/by-nc/3.0/ It is identical to the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) |
spellingShingle | Original Article Chang, Youjin Kim, Seon Ye Choi, Yun Jung So, Kwang Sup Rho, Jin Kyung Kim, Woo Sung Lee, Jae Cheol Chung, Jin-Haeng Choi, Chang-Min Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
title | Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
title_full | Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
title_fullStr | Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
title_full_unstemmed | Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
title_short | Neuroendocrine Differentiation in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor |
title_sort | neuroendocrine differentiation in acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790027/ https://www.ncbi.nlm.nih.gov/pubmed/24101933 http://dx.doi.org/10.4046/trd.2013.75.3.95 |
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