Intracytoplasmic epidermal growth factor receptor shows poor response to the cetuximab antitumor effect in irradiated non-small cell lung cancer cell lines.
OBJECTIVE
The purpose of this study was to evaluate the antitumor effect of a blocking antibody for EGFR in the cytoplasm of a lung cancer cell line.


METHODS
The A549 and H1299 cell lines were employed to demonstrate differential responses to cetuximab in combination with radiotherapy. Localization of EGFR was detected using confocal microscopy, and radiosensitivity was measured.


RESULTS
Treatment with cetuximab inhibited colony formation in a dose-dependent manner in A549, but not H1299 cells. Confocal microscopy revealed EGFR localized in the cytosolic fraction, particularly around the golgi apparatus in H1299, in contrast to cell membrane localization in A549 cell line. After irradiation, nuclear EGFR was detected in the A549 cell line. However, EGFR did not translocate to the nucleus in H1299 cells. While EGFR expression was decreased in both A549 and H1299 cell lines upon treatment with a combination of cetuximab and radiation, radiosensitivity was increased solely in A549 cells.


CONCLUSIONS
Our findings suggest that localization of EGFR is related to the sensitivity/resistance of cells to a combination of cetuximab and radiotherapy.
Department of Radiation Oncology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Seung-Hee
SH
Ryu
Sang-Wook
SW
Lee
Youn-Joo
YJ
Yang
Si Yeol
SY
Song
Jong Hoon
JH
Kim
Eun Kyung
EK
Choi
Seung Do
SD
Ahn
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D000068818:Cetuximab; D059248:Chemoradiotherapy; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011836:Radiation Tolerance
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab