Augmented expression of cardiac ankyrin repeat protein is induced by pemetrexed and a possible marker for the pemetrexed resistance in mesothelioma cells

• 関根, 郁夫

• Qin, Yiyang

• Sekine, Ikuo

• Fan, Mengmeng

• Takiguchi, Yuichi

• Tada, Yuji

• Shingyoji, Masato

• Hanazono, Michiko

• Yamaguchi, Naoto

• Tagawa, Masatoshi

抄録

Background Pemetrexed (PEM) is an anti-cancer agent targeting DNA and RNA synthesis, and clinically in use for mesothelioma and non-small cell lung carcinoma. A mechanism of resistance to PEM is associated with elevated activities of several enzymes involved in nucleic acid metabolism. Methods We established two kinds of PEM-resistant mesothelioma cells which did not show any increase of the relevant enzyme activities. We screened genes enhanced in the PEM-resistant cells with a microarray analysis and confirmed the expression levels with Western blot analysis. A possible involvement of the candidates in the PEM-resistance was examined with a WST assay after knocking down the expression with si-RNA. We also analyzed a mechanism of the up-regulated expression with agents influencing AMP-activated protein kinase (AMPK) and p53. Results We found that expression of cardiac ankyrin repeat protein (CARP) was elevated in the PEM-resistant cells with a microarray and Western blot analysis. Down-regulation of CARP expression with si-RNA did not however influence the PEM resistance. Parent and PEM-resistant cells treated with PEM increased expression of CARP, AMPK, p53 and histone H2AX. The CARP up-regulation was however irrelevant to the p53 genotypes and not induced by an AMPK activator. Augmented p53 levels with nutlin-3a, an inhibitor for p53 degradation, and DNA damages were not always associated with the enhanced CARP expression. Conclusions These data collectively suggest that up-regulated CARP expression is a potential marker for development of PEM-resistance in mesothelioma and that the PEM-mediated enhanced expression is not directly linked with immediate cellular responses to PEM.

収録刊行物

• Cancer cell international

  Cancer cell international 17 120-, 2017-12

  BioMed Central

キーワード

• Cancer Research
• Genetics
• Oncology

詳細情報

• CRID: 1050282677603486720
• NII論文ID: 120007134581
• NII書誌ID: AA12050420
• ISSN: 14752867
• DOI: 10.1186/s12935-017-0493-8
• HANDLE: 2241/00150718
• Web Site: https://tsukuba.repo.nii.ac.jp/records/45441
• Web Site: http://link.springer.com/content/pdf/10.1186/s12935-017-0493-8.pdf
• Web Site: http://link.springer.com/article/10.1186/s12935-017-0493-8/fulltext.html
• 本文言語コード: en
• 資料種別: journal article
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