Abstract 340: ABI1 and androgen dependence in prostate cancer
Tumor Biology(2020)
摘要
Background: Androgen independence is the most challenging problem in the treatment of advanced prostate cancer. Although most patients with early-stage prostate cancer can be cured with surgical and/or radiation treatment, the remainder of patients ultimately recur with metastatic disease upon development of resistance to anti-androgen therapy. Epithelial mesenchymal transition (EMT) and lineage plasticity has been proposed as key mechanisms underlying resistance in treatment-induced prostate cancer with neuroendocrine features (NEPC). There has been a rise in treatment-induced NEPC with increased use of anti-androgen therapies. ABI1 regulates EMT by suppressing FYN-STAT3 activation downstream from noncanonical WNT pathway, but the interaction of ABI1 with androgen pathway is not known. We sought to determine the effect of neoadjuvant hormone treatment (NHT) on ABI1 expression levels in different tumor types. Methods: Here we analyzed ABI1 expression (IHC) in tissue microarray containing 75 tumors with no prior treatment, 198 patients subjected to NHT prior to surgery and 39 castration resistant tumors (total n=307). Androgen-induced ABI1 expression was determined upon R1881 treatment by Western blotting and immunofluorescence in hormone- sensitive LNCaP cells. Results: ABI1 expression was significantly downregulated in tumors from patients undergoing NHT(p Conclusion:ABI1 is an androgen sensitive gene. ABI1 expression is increased in CRPC, most likely secondary to androgen receptor reactivation. It is subsequently downregulated in NEPC, hence, we hypothesize that this may be a key mechanism driving the NEPC phenotype through promoting EMT. Further understanding of the role ABI1 may play in this transformation will provide a more mechanistic understanding of prostate cancer progression and maylead to improved targeted treatment options. Citation Format: Leszek Kotula, Baylee A. Porter, Xiang Li, Maria A. Ortiz, Rakesh Khanna, Fan Zhang, Sonia H. Kung, Ladan Fazli, Martin E. Gleave, Gennady Bratslavsky, Jeffrey S. Ross. ABI1 and androgen dependence in prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 340.
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