Overexpression of CTEN is associated with gefitinib resistance in non‑small cell lung cancer

Lu,Xiangdong; Zhang,Yao; Pan,Yukai; Cao,Minmin; Zhou,Xie; Zhang,Tingrong

doi:10.3892/ol.2020.12301

Overexpression of CTEN is associated with gefitinib resistance in non‑small cell lung cancer

Authors:
- Xiangdong Lu
- Yao Zhang
- Yukai Pan
- Minmin Cao
- Xie Zhou
- Tingrong Zhang
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Affiliations: Department of Oncology, The Jiangyin Hospital Affiliated to Medical College of Southeast University, Jiangyin, Jiangsu 214400, P.R. China
Published online on: November 13, 2020 https://doi.org/10.3892/ol.2020.12301
Article Number: 40
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

COOH‑terminus tensin‑like molecule (CTEN) is a member of the tensin family, which is considered to be one of the novel proto‑oncogenes involved in tumorigenesis and cancer progression. However, the mechanisms of CTEN in acquired resistance of non‑small cell lung cancer (NSCLC) remain relatively unknown. The aim of the present study was to understand the roles of CTEN in acquired gefitinib resistance of NSCLC. The present study investigated the expression level of CTEN using reverse transcription‑quantitative polymerase chain reaction and Western blot analysis. Cell Counting kit‑8 and colony‑formation assays were performed to evaluate the proliferative and colony‑formative abilities of PC9 and PC9/GR cells in vitro. Mouse xenograft models were used to assess the growth of PC9/GR cells in vivo. A gefitinib‑resistant NSCLC cell line (PC9/GR) was established, and the protein and mRNA expression levels of CTEN were observed to be higher in PC9/GR cells than in PC9 cells. Notably, the sensitivity of PC9/GR cells to gefitinib was observed to be decreased when CTEN was overexpressed, while PC9/GR cells with CTEN‑downregulation showed markedly enhanced sensitivity to gefitinib. In vitro proliferation and colony formation assays revealed that increased CTEN markedly promoted the cell proliferative and colony‑forming capacities of PC9 and PC9/GR cells, and CTEN‑silencing inhibited the cell proliferative and colony‑forming abilities of the PC9 and PC9/GR cells. Notably, deficient expression of CTEN notably retarded the growth of PC9/GR xenografts in vivo. In addition, the plasma mRNA expression of CTEN was notably elevated in patients with NSCLC with acquired gefitinib resistance. Overexpression of CTEN is associated with acquired gefitinib resistance in NSCLC. CTEN may be investigated as a potential therapeutic target for the treatment of patients with NSCLC with acquired gefitinib resistance.

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