04 October 2018 : Clinical Research
Expression of Androgen Receptor Variant 7 (AR-V7) in Circulated Tumor Cells and Correlation with Drug Resistance of Prostate Cancer CellsShuaibin Wang1AC, Sen Yang1BD, Cunjin Nan1CE, Yijun Wang1DF, Youhua He1EG, Haiqi Mu1DG
Med Sci Monit 2018; 24: CLR7051-7056
BACKGROUND: Prostate cancer is a common type of malignant tumor invading the male reproductive-urinary system, which has increasing incidence worldwide. Androgen receptor variant 7 (AR-V7) participates in regulating prostate cancer cell proliferation and gene expression. This study aimed to investigate the expression of AR-V7 in circulated tumor cells (CTCs) in patients with prostate cancer and to assess its correlation with drug sensitivity against enzalutamide or abiraterone.
MATERIAL AND METHODS: Blood samples of prostate cancer patients were collected for separating CTCs, in which mRNA expression level of full-length AR and AR-V7 was measured to analyze their correlation with enzalutamide or abiraterone resistance. Progression-free survival (PFS) of patients with different AR-V7 expression levels was compared. AR-V7 was overexpressed in transfected prostate cancer cells, and its effects on proliferation were analyzed by clonal formation assay.
RESULTS: qRT-PCR showed AR-V7 overexpression in a total of 13 patients; 76.92% of these patients developed drug resistance, the distal metastasis of which was significantly higher than that in the group with AR-V7 downregulation, with lower PFS (p<0.01). In cultured prostate cancer cells, AR-V7 upregulation resulted in a significantly higher clonal formation rate than in the control group with enzalutamide-containing medium (p<0.05).
CONCLUSIONS: In prostate cancer cells, AR-V7 expression is correlated with drug resistance, as AR-V7 upregulation leads to enhanced proliferation potency of cancer cells, indicating unfavorable prognosis of patients.
Keywords: Drug Resistance, Prostate, Prostatic Diseases
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