ArticleCancer science2005
Characterization of human NSCLC cell line with innate etoposide-resistance mediated by cytoplasmic localization of topoisomerase II alpha.
Article in Cancer science, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Chemoresistance Mechanisms in Non-Small Cell Lung Cancer-Opportunities for Drug Repurposing.Applied biochemistry and biotechnology · 2024Review
- The correlation study between TOP2A gene expression in circulating tumor cells and chemotherapeutic drug resistance of patients with breast cancer.Breast cancer (Tokyo, Japan) · 2024Article
- Mechanisms of resistance to chemotherapy in non-small cell lung cancer.Archives of pharmacal research · 2021Review
- Multidrug resistance characterization in multicellular tumour spheroids from two human lung cancer cell lines.Cancer cell international · 2015Article
- Overexpression of MEOX2 and TWIST1 is associated with H3K27me3 levels and determines lung cancer chemoresistance and prognosis.PloS one · 2014Article
- Mouse mammary tumor virus-like gene sequences are present in lung patient specimens.Virology journal · 2011Article
- Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer.Critical reviews in oncology/hematology · 2010Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Topoisomerase (topo) II alpha is a target for many chemotherapeutic agents in clinical use. In tumor cells resistant to topo II poisons, there have been descriptions of quantitative and qualitative alterations involved in this enzyme. More recently, the cytoplasmic localization of topo II alpha has been described as a mechanism to confer drug resistance. Here, we report the characterization of a human non-small-cell lung cancer cell line, INER-37, which shows an innate resistance to etoposide. In this cell line, etoposide resistance was directly associated with the expression of topo II alpha resident mainly in the cytoplasmic region. At the molecular level, INER-37 cells carry on a heterozygous gene deletion, transcribing two different topo II alpha mRNAs: 4.8 kb and 2.0 kb. The bigger 4.8 kb mRNA (missing 1.3 kb of 3' mRNA and including the untranslated region) is translated into a truncated cytoplasmic protein of approximately 160 kDa. The protein truncation affects at least 96 amino acids in the COOH-terminal region where the more proximal bipartite nuclear localization signal is located. The INER-37 cell line is the first cancer cell line reported with an innate mutation affecting the 3'-end region of the topo II alpha gene that confers a cytoplasmic localization of the enzyme and therefore an increased resistance to etoposide.
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