A new human lung adenocarcinoma cell line harboring the EML4-ALK fusion gene

Hideko Isozaki, Masayuki Yasugi, Nagio Takigawa, Katsuyuki Hotta, Eiki Ichihara, Akihiko Taniguchi, Shinichi Toyooka, Shinsuke Hashida, Toshiaki Sendo, Mitsune Tanimoto, Katsuyuki Kiura

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

OBJECTIVE: The echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was identified in patients with non-small cell lung cancer. To the best of our knowledge, there are only three cell lines harboring the EML4-ALK fusion gene, which have contributed to the development of therapeutic strategies. Therefore, we tried to establish a new lung cancer cell line harboring EML4-ALK.

METHODS: A 61-year-old Japanese female presented with chest discomfort. She was diagnosed with left lung adenocarcinoma with T4N3M1 Stage IV. Although she was treated with chemotherapy, her disease progressed with massive pleural effusion. Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib. She did well for 3 months.

RESULTS: Tumor cells were obtained from the malignant pleural effusion before treatment with crizotinib. Cells continued to proliferate substantially for several weeks. The cell line was designated ABC-11. The EML4-ALK fusion protein and genes were identified in ABC-11 cells using fluorescence in situ hybridization and immunohistochemistry, respectively. ABC-11 cells were sensitive to crizotinib and next-generation ALK inhibitors (ceritinib and AP26113), as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Phosphorylated ALK protein and its downstream signaling were suppressed by treatment with crizotinib in western blotting. Furthermore, we could transplant ABC-11 cells subcutaneously into BALB/c nu/nu mice.

CONCLUSIONS: We successfully established a new lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. This cell line could contribute to future research of EML4-ALK-positive lung cancer both in vivo and in vitro.

Original languageEnglish
Pages (from-to)963-968
Number of pages6
JournalJapanese Journal of Clinical Oncology
Volume44
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Gene Fusion
Cell Line
Fluorescence In Situ Hybridization
Lung Neoplasms
Malignant Pleural Effusion
Adenocarcinoma of lung
MAP4
anaplastic lymphoma kinase
Pleural Effusion
Non-Small Cell Lung Carcinoma
Proteins
Thorax
Therapeutics
Western Blotting
Immunohistochemistry
Transplants
Drug Therapy
crizotinib

Keywords

  • crizotinib
  • EML4-ALK
  • lung cancer

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A new human lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. / Isozaki, Hideko; Yasugi, Masayuki; Takigawa, Nagio; Hotta, Katsuyuki; Ichihara, Eiki; Taniguchi, Akihiko; Toyooka, Shinichi; Hashida, Shinsuke; Sendo, Toshiaki; Tanimoto, Mitsune; Kiura, Katsuyuki.

In: Japanese Journal of Clinical Oncology, Vol. 44, No. 10, 01.10.2014, p. 963-968.

Research output: Contribution to journalArticle

@article{df07494413a84dc387abad7667697062,
title = "A new human lung adenocarcinoma cell line harboring the EML4-ALK fusion gene",
abstract = "OBJECTIVE: The echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was identified in patients with non-small cell lung cancer. To the best of our knowledge, there are only three cell lines harboring the EML4-ALK fusion gene, which have contributed to the development of therapeutic strategies. Therefore, we tried to establish a new lung cancer cell line harboring EML4-ALK.METHODS: A 61-year-old Japanese female presented with chest discomfort. She was diagnosed with left lung adenocarcinoma with T4N3M1 Stage IV. Although she was treated with chemotherapy, her disease progressed with massive pleural effusion. Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib. She did well for 3 months.RESULTS: Tumor cells were obtained from the malignant pleural effusion before treatment with crizotinib. Cells continued to proliferate substantially for several weeks. The cell line was designated ABC-11. The EML4-ALK fusion protein and genes were identified in ABC-11 cells using fluorescence in situ hybridization and immunohistochemistry, respectively. ABC-11 cells were sensitive to crizotinib and next-generation ALK inhibitors (ceritinib and AP26113), as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Phosphorylated ALK protein and its downstream signaling were suppressed by treatment with crizotinib in western blotting. Furthermore, we could transplant ABC-11 cells subcutaneously into BALB/c nu/nu mice.CONCLUSIONS: We successfully established a new lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. This cell line could contribute to future research of EML4-ALK-positive lung cancer both in vivo and in vitro.",
keywords = "crizotinib, EML4-ALK, lung cancer",
author = "Hideko Isozaki and Masayuki Yasugi and Nagio Takigawa and Katsuyuki Hotta and Eiki Ichihara and Akihiko Taniguchi and Shinichi Toyooka and Shinsuke Hashida and Toshiaki Sendo and Mitsune Tanimoto and Katsuyuki Kiura",
year = "2014",
month = "10",
day = "1",
doi = "10.1093/jjco/hyu110",
language = "English",
volume = "44",
pages = "963--968",
journal = "Japanese Journal of Clinical Oncology",
issn = "0368-2811",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - A new human lung adenocarcinoma cell line harboring the EML4-ALK fusion gene

AU - Isozaki, Hideko

AU - Yasugi, Masayuki

AU - Takigawa, Nagio

AU - Hotta, Katsuyuki

AU - Ichihara, Eiki

AU - Taniguchi, Akihiko

AU - Toyooka, Shinichi

AU - Hashida, Shinsuke

AU - Sendo, Toshiaki

AU - Tanimoto, Mitsune

AU - Kiura, Katsuyuki

PY - 2014/10/1

Y1 - 2014/10/1

N2 - OBJECTIVE: The echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was identified in patients with non-small cell lung cancer. To the best of our knowledge, there are only three cell lines harboring the EML4-ALK fusion gene, which have contributed to the development of therapeutic strategies. Therefore, we tried to establish a new lung cancer cell line harboring EML4-ALK.METHODS: A 61-year-old Japanese female presented with chest discomfort. She was diagnosed with left lung adenocarcinoma with T4N3M1 Stage IV. Although she was treated with chemotherapy, her disease progressed with massive pleural effusion. Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib. She did well for 3 months.RESULTS: Tumor cells were obtained from the malignant pleural effusion before treatment with crizotinib. Cells continued to proliferate substantially for several weeks. The cell line was designated ABC-11. The EML4-ALK fusion protein and genes were identified in ABC-11 cells using fluorescence in situ hybridization and immunohistochemistry, respectively. ABC-11 cells were sensitive to crizotinib and next-generation ALK inhibitors (ceritinib and AP26113), as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Phosphorylated ALK protein and its downstream signaling were suppressed by treatment with crizotinib in western blotting. Furthermore, we could transplant ABC-11 cells subcutaneously into BALB/c nu/nu mice.CONCLUSIONS: We successfully established a new lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. This cell line could contribute to future research of EML4-ALK-positive lung cancer both in vivo and in vitro.

AB - OBJECTIVE: The echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was identified in patients with non-small cell lung cancer. To the best of our knowledge, there are only three cell lines harboring the EML4-ALK fusion gene, which have contributed to the development of therapeutic strategies. Therefore, we tried to establish a new lung cancer cell line harboring EML4-ALK.METHODS: A 61-year-old Japanese female presented with chest discomfort. She was diagnosed with left lung adenocarcinoma with T4N3M1 Stage IV. Although she was treated with chemotherapy, her disease progressed with massive pleural effusion. Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib. She did well for 3 months.RESULTS: Tumor cells were obtained from the malignant pleural effusion before treatment with crizotinib. Cells continued to proliferate substantially for several weeks. The cell line was designated ABC-11. The EML4-ALK fusion protein and genes were identified in ABC-11 cells using fluorescence in situ hybridization and immunohistochemistry, respectively. ABC-11 cells were sensitive to crizotinib and next-generation ALK inhibitors (ceritinib and AP26113), as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Phosphorylated ALK protein and its downstream signaling were suppressed by treatment with crizotinib in western blotting. Furthermore, we could transplant ABC-11 cells subcutaneously into BALB/c nu/nu mice.CONCLUSIONS: We successfully established a new lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. This cell line could contribute to future research of EML4-ALK-positive lung cancer both in vivo and in vitro.

KW - crizotinib

KW - EML4-ALK

KW - lung cancer

UR - http://www.scopus.com/inward/record.url?scp=84922392467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922392467&partnerID=8YFLogxK

U2 - 10.1093/jjco/hyu110

DO - 10.1093/jjco/hyu110

M3 - Article

VL - 44

SP - 963

EP - 968

JO - Japanese Journal of Clinical Oncology

JF - Japanese Journal of Clinical Oncology

SN - 0368-2811

IS - 10

ER -