期刊
TRANSLATIONAL ONCOLOGY
卷 34, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2023.101698
关键词
ARV7; Androgen receptor; FOXA1; IGFBP-2; Chemotherapy; Prostate cancer
类别
Prostate cancer is a leading cause of cancer-related deaths in men, and the progression of the disease may be influenced by alternative splicing of the androgen receptor, particularly the AR variant 7(ARV7). ARV7-positive prostate cancer cells were found to be less sensitive to treatment and exhibited increased cell division, proliferation, and motility compared to ARV7-negative cells. Additionally, protein analysis showed a correlation between ARV7 and insulin-like growth factor-2 (IGFBP-2) and forkhead box protein A1(FOXA1), suggesting an interplay between these factors in the acquisition of an aggressive prostate cancer phenotype.
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Localised PCa can be treated effectively, but most patients relapse/progress to more aggressive disease. One possible mechanism underlying this progression is alternative splicing of the androgen receptor, with AR variant 7(ARV7) considered to play a major role. Using viability assays, we confirmed that ARV7-positive PCa cells were less sensitive to treatment with cabazitaxel and an anti-androgen-enzalutamide. Also, using live-holographic imaging, we showed that PCa cells with ARV7 exhibited an increased rate of cell division, proliferation, and motility, which could potentially contribute to a more aggressive phenotype. Furthermore, protein analysis demonstrated that ARV7 knock-down was associated with a decrease in insulin-like growth factor-2 (IGFBP-2) and forkhead box protein A1(FOXA1). This correlation was confirmed in-vivo using PCa tissue samples. Spearman rank correlation analysis showed significant positive associations between ARV7 and IGFBP-2 or FOXA1 in tissue from patients with PCa. This association was not present with the AR. These data suggest an interplay of FOXA1 and IGFBP-2 with ARV7mediated acquisition of an aggressive prostate cancer phenotype.
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