Low expression of phosphatase and tensin homolog in clear‑cell renal cell carcinoma contributes to chemoresistance through activating the Akt/HDM2 signaling pathway

Chen,Jun; Zhu,He; Zhang,Yan; Cui,Man‑Hua; Han,Li‑Ying; Jia,Zhan‑Hui; Wang,Ling; Teng,Hong; Miao,Li‑Ning

doi:10.3892/mmr.2015.3740

Low expression of phosphatase and tensin homolog in clear‑cell renal cell carcinoma contributes to chemoresistance through activating the Akt/HDM2 signaling pathway

Authors:
- Jun Chen
- He Zhu
- Yan Zhang
- Man‑Hua Cui
- Li‑Ying Han
- Zhan‑Hui Jia
- Ling Wang
- Hong Teng
- Li‑Ning Miao
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Affiliations: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: May 7, 2015 https://doi.org/10.3892/mmr.2015.3740
Pages: 2622-2628
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Clear‑cell renal cell carcinoma (CCRCC) is the most frequent primary malignancy in the adult kidney. Most patients with advanced CCRCC have poor prognosis as CCRCC remains resistant to chemotherapy. The present study explored the possible mechanism underlying CCRCC resistance to chemotherapy and found that loss of PTEN in CCRCC may be involved. Knockdown of PTEN in the CCRCC cell line ACHN blocked etoposide‑induced apoptosis and etoposide‑impaired cell proliferation was also inhibited. It has been demonstrated that most chemotherapy drugs exert their anti-cancer effects via p53‑mediated apoptosis, and in accordance, with this, the present study showed that treatment with etoposide significantly increased p53 levels. Silencing of PTEN in ACHN inhibited the Akt/HDM2 signaling cascade and depressed p53 expression, and the interaction between HDM2 and p53 was also enhanced. This was further verified in CCRCC tissue specimens from patients The results of the present study suggested that loss of PTEN, which deactivated Akt/HDM2 signaling followed by degradation of p53, may contribute to the development of etoposide resistance in CCRCC.

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