title: Low expression of phosphatase and tensin homolog in clear‑cell renal cell carcinoma contributes to chemoresistance through activating the Akt/HDM2 signaling pathway.
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.
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Man-Hua
authors.initials: MH
authors.lastname: Cui
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Han
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Zhan-Hui
authors.initials: ZH
authors.lastname: Jia
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Teng
authors.affiliation: Department of Nephrology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Li-Ning
authors.initials: LN
authors.lastname: Miao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics*; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human