A newly established monoclonal antibody against ERCC1 detects major isoforms of ERCC1 in gastric cancer.

Autor: Oishi T; Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.; Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Sasaki Y; Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.; Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Tong Y; Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Chen L; Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Onodera T; Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.; Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Iwasa S; Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan., Udo E; Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, Nagasaki, Japan., Furusato B; Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, Nagasaki, Japan., Fujimori H; Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Imamichi S; Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan., Honda T; Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Bessho T; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA., Fukuoka J; Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Ashizawa K; Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, Nagasaki, Japan.; Department of Clinical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Yanagihara K; Division of Biomarker Discovery, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan., Nakao K; Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Yamada Y; Department of Medical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan.; Comprehensive Cancer Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan., Hiraoka N; Division of Pathology, National Cancer Center Hospital, Tokyo, Japan., Masutani M; Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.; Laboratory of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.; Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Jazyk: angličtina
Zdroj: Global health & medicine [Glob Health Med] 2021 Aug 31; Vol. 3 (4), pp. 226-235.
DOI: 10.35772/ghm.2021.01001
Abstrakt: Identifying patients resistant to cisplatin treatment is expected to improve cisplatin-based chemotherapy for various types of cancers. Excision repair cross-complementing group 1 (ERCC1) is involved in several repair processes of cisplatin-induced DNA crosslinks. ERCC1 overexpression is reported as a candidate prognostic factor and considered to cause cisplatin resistance in major solid cancers. However, anti-ERCC1 antibodies capable of evaluating expression levels of ERCC1 in clinical specimens were not fully optimized. A mouse monoclonal antibody against human ERCC1 was generated in this study. The developed antibody 9D11 specifically detected isoforms of 201, 202, 203 but not 204, which lacks the exon 3 coding region. To evaluate the diagnostic usefulness of this antibody, we have focused on gastric cancer because it is one of the major cancers in Japan. When ERCC1 expression was analyzed in seventeen kinds of human gastric cancer cell lines, all the cell lines were found to express either 201, 202, and/or 203 as major isoforms of ERCC1, but not 204 by Western blotting analysis. Immunohistochemical staining showed that ERCC1 protein was exclusively detected in nuclei of the cells and a moderate level of constant positivity was observed in nuclei of vascular endothelial cells. It showed a clear staining pattern in clinical specimens of gastric cancers. Antibody 9D11 may thus be useful for estimating expression levels of ERCC1 in clinical specimens.
Competing Interests: Takuya Honda was endowed by Eli Lilly Japan K.K.. Other authors have no conflicts of interest to disclose.
(2021, National Center for Global Health and Medicine.)
Databáze: MEDLINE