STAT3 and STAT5A are Potential Therapeutic Targets in Castration-Resistant Prostate Cancer

Collection:
Clark Atlanta University Faculty Publications
Title:
STAT3 and STAT5A are Potential Therapeutic Targets in Castration-Resistant Prostate Cancer
Creator:
Mohanty, Sambit K.
Yagiz, Kader
,Pradhan, Dinesh
Luthringer, Daniel J.
Amin, Mahul B.
Alkan, Serhan
Cinar, Bekir
Date of Original:
2017-09-12
Subject:
African Americans--Education (Higher)--Georgia
Clark Atlanta University
Location:
United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
Medium:
articles
Type:
Text
Format:
application/pdf
Description:
Abstract: Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH). We demonstrated that PC cells express varying levels of STAT3 and STAT5A transcripts. In addition, we demonstrate that pimozide, a psychotropic drug and an indirect inhibitor of STAT5, attenuated PC cells growth, and induced apoptosis in a dose-dependent manner. Furthermore, our analysis of the PC public data revealed that the STAT3/5A genes were frequently amplified in metastatic CRPC. These findings suggest that STAT3/5A potentially serves as a predictive biomarker to evaluate the therapeutic efficacy of a cancer drug targeting the JAK/STAT pathway. Since the JAK/STAT and AR pathways are suggested to be functionally synergistic, inhibition of the JAK/STAT signaling alone or together with AR may lead to a novel treatment modality for patients with advanced PC.
Source: Oncotarget. 2017; 8:85997-8601
DOI: 10.18632/oncotarget.20844
Metadata URL:
http://hdl.handle.net/20.500.12322/cau.ir:2017_cinar
Language:
eng
Original Collection:
Clark Atlanta University Faculty Publications
Holding Institution:
Clark Atlanta University
Rights:

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