Interactions between androgen receptor signaling and other molecular pathways in prostate cancer progression: Current and future clinical implications

Pisano, Chiara; Tucci, Marco; Stefano, Rosario Francesco Di; Turco, Fabio; Scagliotti, Giorgio Vittorio; Maïo, Massimo Di; Buttigliero, Consuelo

doi:10.1016/j.critrevonc.2020.103185

Cited by 51 publications

(55 citation statements)

References 137 publications

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“…5). These pathways are known to be dysregulated in multiple cancer types including hormone independent melanoma and non-melanoma skin cancers and are often targets for chemotherapeutic intervention (Chan et al 2018 ; Dika et al 2019 ; Hua et al 2018 ; Karayazi Atici et al 2020 ; Mal et al 2020 ; Pisano et al 2021 ; Porter et al 2019 ; Rajabi et al 2017 ; Xiao et al 2019 ). As 3+ exposure at the environmentally relevant level of 100 nM for 48 h was found to suppress the expression of ERα mRNA and protein in MCF-7 cells and bind competitively to its hormone binding domain with K i of 5 nM, modulating its downstream signaling (Davey et al 2007 ; Stoica et al 2000 ; Watson and Yager 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

et al. 2021

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Chronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.

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Section: Discussionmentioning

confidence: 99%

Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

et al. 2021

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“…The unrestrained cell cycle progression had been regarded as a feature of human cancer. Interestingly, we found multiple cell cycle regulators were up-regulated in PCa, including CCNB1, CCNB2, PLK1, TTK, AURKA, CDC20, BUB1, PTTG1, CDC45, CDC25C, CCNA2, and BUB1B [ 20 – 26 ]. Previous studies had shown that these genes functioned crucially in cell cycle progression and were dysregulated in human cancers.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Analysis Reveals Key Genes and Signalings Associated with the Prognosis of Prostate Cancer

Shen

Guo

et al. 2021

Computational and Mathematical Methods in Medicine

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It is urgent to identify novel biomarkers for prostate cancer (PCa) prognosis and to understand the mechanisms regulating the tumorigenesis for PCa treatment. In this study, GSE17951 and TCGA were used to identify the differentially expressed genes (DEGs). Our study demonstrated that 1533 genes with increased expression and 2301 genes with decreased expression in PCa. Bioinformatics analysis data indicated that these up-regulated genes had an association with the modulation of mitotic nuclear division, sister chromatid cohesion, cell division, and cell cycle. Additionally, our results revealed downregulated genes took part in modulating extracellular matrix organization, angiogenesis, signal transduction, and Ras signaling pathway. Hub upregulated and downregulated PPI networks were identified by protein-protein interaction (PPI) network analysis and MCODE analysis. Of note, 12 cell cycle regulators, comprising CCNB1, CCNB2, PLK1, TTK, AURKA, CDC20, BUB1, PTTG1, CDC45, CDC25C, CCNA2, and BUB1B, were demonstrated to function crucially in PCa development. By detecting their expression in PCa cell lines, we confirmed that these cell cycle regulator expressions were heightened in PCa cells. GEPIA databases analysis showed that higher expression of these cell cycle regulators was correlated to shorter disease-free survival (DFS) time in PCa samples. Our findings collectively suggested targeting cell cycle pathways may offer novel prognosis and treatment biomarkers for PCa.

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“…Another important factor relates to the activity of the androgen pathway, as the signaling pathway mediated by AR plays a central role in the prostate gland's development and function. Studies using conventional approaches and next-generation sequencing (NGS) have revealed that a majority of primary and metastatic prostate cancers harbors genomic alterations in the androgen signaling pathway, including AR amplification/mutations, gain of AR nuclear receptor coactivator 1/2 (NCOA1/2), and loss of AR nuclear receptor corepressor 1/2 (NCOR1/2) which contributes to castration resistance (46). In addition, AR genomic structural rearrangements are present in one-third of mCRPC tumors, resulting in aberrant expression of diverse AR variant species lacking the ligand-binding domain and resulting in persistent activation of AR signaling, such as AR variant 7 (AR-V7), which appears to drive disease progression (47,48).…”

Section: Genetics Of Prostate Carcinomamentioning

confidence: 99%

Genetics of Prostate Carcinoma

Krušlin

Škara

Vodopić

et al. 2021

ama

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The aim of this review is to provide a brief overview of some current approaches regarding diagnostics, pathologic features, treatment, and genetics of prostate carcinoma (PCa). Prostate carcinoma is the most common visceral tumor and the second most common cancer-related cause of death in males. Clinical outcomes for patients with localized prostate cancer are excellent, but despite advances in prostate cancer treatments, castrate-resistant prostate cancer and metastatic prostate cancer patients have a poor prognosis. Advanced large-scale genomic studies revealed a large number of genetic alterations in prostate cancer. The meaning of these alterations needs to be validated in the specific prostate cancer molecular subtype context. Along these lines, there is a critical need for establishing genetically engineered mouse models, which would include speckle type BTB/POZ protein and isocitrate Dehydrogenase (NADP (+)) 1 mutant, as well as androgen receptor neuroendocrine subtypes of prostate cancer. Another urgent need is developing highly metastatic prostate cancer models, as only up to 17% of available models dis- play bone metastases and exhibit a less typical neuroendocrine prostate cancer or sarcomatoid carcinoma. Moreover, androgen deprivation and relapse should be mimicked in the genetically engineered mouse models, as androgen independence may yield a better model for metastatic castrate-resistant prostate cancer. The development of such refined animal models should be guid- ed by comparative genomics of primary versus corresponding metastatic tumors. Such an approach will have the potential to illuminate the key genetic events associated with specific molecular prostate cancer subsets and indicate directions for effective therapy.Conclusion. Despite excellent results in the treatment of localized prostatic carcinoma, castrate-resistant prostate can- cer and metastatic prostate cancer have a poor prognosis. Advanced large-scale genomic studies revealed a large number of ge- netic alterations in PCa. Experimental models of prostate carcinoma in genetically modified mice could provide new data about the genetic changes in such cancers and help in developing better animal models for treatment resistant prostate carcinomas.

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Interactions between androgen receptor signaling and other molecular pathways in prostate cancer progression: Current and future clinical implications

Cited by 51 publications

References 137 publications

Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

Gene Expression Analysis Reveals Key Genes and Signalings Associated with the Prognosis of Prostate Cancer

Genetics of Prostate Carcinoma

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