scholarly journals ETS fusion genes in prostate cancer

2014 ◽  
Vol 21 (3) ◽  
pp. R143-R152 ◽  
Author(s):  
Delila Gasi Tandefelt ◽  
Joost Boormans ◽  
Karin Hermans ◽  
Jan Trapman
Keyword(s):  
Prostate Cancer ◽  
Transcription Factors ◽  
Current Knowledge ◽  
Tumor Development ◽  
Developed Countries ◽  
Genomic Alteration ◽  
Gene Fusions ◽  
Ets Transcription Factors ◽  
Progressive Growth

Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostate-specific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2–ERG and other ETS gene fusions in prostate cancer.

scholarly journals Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour

2021 ◽  
Vol 22 (11) ◽  
pp. 5560
Author(s):  
Alejandro Álvarez-Artime ◽  
Belén García-Soler ◽  
Rosa María Sainz ◽  
Juan Carlos Mayo
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Tumor Development ◽  
Cell Types ◽  
Protective Role ◽  
Bioactive Molecules ◽  
Brown Adipose ◽  
Endocrine Organs

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.

scholarly journals CHEK2∗1100delC Mutation and Risk of Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Victoria Hale ◽  
Maren Weischer ◽  
Jong Y. Park
Keyword(s):  
Prostate Cancer ◽  
Current Knowledge ◽  
Prostate Cancer Screening ◽  
Critical Role ◽  
Prostate Cancer Risk ◽  
Conclusive Evidence ◽  
Increased Risk ◽  
History Of ◽  
Cancer Studies

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

scholarly journals The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1887 ◽  
Author(s):  
Francesco Bonollo ◽  
George N. Thalmann ◽  
Marianna Kruithof-de Julio ◽  
Sofia Karkampouna
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Progression ◽  
Normal Prostate ◽  
Prostate Tumorigenesis

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa.

scholarly journals Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics

2020 ◽  
Vol 21 (8) ◽  
pp. 2991 ◽  
Author(s):  
Phuong Kim To ◽  
Manh Hung Do ◽  
Jin-Hyoung Cho ◽  
Chaeyong Jung
Keyword(s):  
Prostate Cancer ◽  
Mammalian Cells ◽  
Tumor Development ◽  
Cancer Therapeutics ◽  
Underlying Mechanism ◽  
Reproductive Organs ◽  
Zinc Homeostasis ◽  
Prostate Cancer Development ◽  
Prostate Cancers

Zinc is a group IIB heavy metal. It is an important regulator of major cell signaling pathways in most mammalian cells, functions as an antioxidant and plays a role in maintaining genomic stability. Zinc deficiency leads to severe diseases in the brain, pancreas, liver, kidneys and reproductive organs. Zinc loss occurs during tumor development in a variety of cancers. The prostate normally contains abundant intracellular zinc and zinc loss is a hallmark of the development of prostate cancer development. The underlying mechanism of this loss is not clearly understood. The knowledge that excess zinc prevents the growth of prostate cancers suggests that zinc-mediated therapeutics could be an effective approach for cancer prevention and treatment, although challenges remain. This review summarizes the specific roles of zinc in several cancer types focusing on prostate cancer. The relationship between prostate cancer and the dysregulation of zinc homeostasis is examined in detail in an effort to understand the role of zinc in prostate cancer.

scholarly journals The emerging role of C/EBPs in glucocorticoid signaling: lessons from the lung

2011 ◽  
Vol 212 (3) ◽  
pp. 291-305 ◽  
Author(s):  
Abraham B Roos ◽  
Magnus Nord
Keyword(s):  
Transcription Factors ◽  
Potential Role ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Steroid Resistance ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Glucocorticoid Signaling ◽  
Enhancer Binding Protein

Glucocorticoids (GCs) have been successfully used in the treatment of inflammatory diseases for decades. However, there is a relative GC resistance in several inflammatory lung disorders, such as chronic obstructive pulmonary disease (COPD), but still the mechanism(s) behind this unresponsiveness remains unknown. Interaction between transcription factors and the GC receptor contribute to GC effects but may also provide mechanisms explaining steroid resistance. CCAAT/enhancer-binding protein (C/EBP) transcription factors are important regulators of pulmonary gene expression and have been implicated in inflammatory lung diseases such as asthma, pulmonary fibrosis, cystic fibrosis, sarcoidosis, and COPD. In addition, several studies have indicated a role for C/EBPs in mediating GC effects. In this review, we discuss the different mechanisms of GC action as well as the function of the lung-enriched members of the C/EBP transcription factor family. We also summarize the current knowledge of the role of C/EBP transcription factors in mediating the effects of GCs, with emphasis on pulmonary effects, and their potential role in mediating GC resistance.

scholarly journals Electrostatic repulsion causes anticooperative DNA binding between tumor suppressor ETS transcription factors and JUN-FOS at composite DNA sites

2018 ◽  
Author(s):  
Bethany J. Madison ◽  
Kathleen A. Clark ◽  
Niraja Bhachech ◽  
Peter C. Hollenhorst ◽  
Barbara J. Graves ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcription Factors ◽  
Dna Binding ◽  
Dna Sequences ◽  
Binding Sites ◽  
Epithelial Cell Line ◽  
Electrostatic Repulsion ◽  
Ets Transcription Factors ◽  
Positively Charged

AbstractMany transcription factors regulate gene expression in a combinatorial fashion often by binding in close proximity on composite cis-regulatory DNA elements. Here we investigate the molecular basis by which ETS transcription factors bind with AP1 transcription factors JUN-FOS at composite DNA-binding sites. The ability to bind to DNA with JUN-FOS correlates with the phenotype of these proteins in prostate cancer: the oncogenic ERG and ETV1/4/5 subfamilies co-occupy ETS-AP1 sites with JUN-FOS in vitro, whereas JUN-FOS robustly inhibits DNA binding by the tumor suppressors EHF and SPDEF. EHF binds to ETS-AP1 DNA with tighter affinity than ERG in the absence of JUN-FOS, which may enable EHF to compete with ERG and JUN-FOS for binding to ETS-AP1 sites. Genome-wide mapping of EHF and ERG binding sites in a prostate epithelial cell line reveal that EHF is preferentially excluded from closely spaced ETS-AP1 DNA sequences. Structural modeling and mutational analyses indicate that adjacent positively-charged surfaces from EHF and JUN-FOS disfavor simultaneous DNA binding due to electrostatic repulsion. The conservation of positively charged residues on the JUN-FOS interface identified ELF1 as an additional ETS factor that exhibits anticooperative DNA binding, and we present evidence that ELF1 is frequently downregulated in prostate cancer. In summary, the divergence of electrostatic features of ETS factors at their JUN-FOS interface enables distinct binding events at ETS-AP1 DNA sequences. We propose that this mechanism can drive unique targeting of ETS transcription factors, thereby facilitating distinct transcriptional programs.

Abstract C95: Role of 5‐alpha reductase inhibitor in regulating ETS transcription factors in prostate cell lines

2009 ◽  
Author(s):  
Bushra Ateeq ◽  
Adaikkalam Vellaichamy ◽  
Arul M. Chiannaiyan ◽  
Sooryanarayana Varambally
Keyword(s):  
Transcription Factors ◽  
Cell Lines ◽  
Reductase Inhibitor ◽  
Prostate Cell ◽  
Ets Transcription Factors ◽  
Prostate Cell Lines

Role of lncRNAs in prostate cancer development and progression

2014 ◽  
Vol 395 (11) ◽  
pp. 1275-1290 ◽  
Author(s):  
Melanie Weiss ◽  
Christoph Plass ◽  
Clarissa Gerhauser
Keyword(s):  
Prostate Cancer ◽  
Target Genes ◽  
Current Knowledge ◽  
Prostate Carcinogenesis ◽  
Prostate Cancer Development ◽  
Chromatin Remodeling Complexes ◽  
Regulation Mechanisms ◽  
Functional Analyses

Abstract Prostate cancer (PCa) is the second most common cause of cancer-related deaths in men. Despite advances in the characterization of genomic and epigenetic aberrations contributing to PCa, the etiology of PCa is still far from being understood. Research over the past decade demonstrated the role of long non-coding RNAs (lncRNAs) in deregulation of target genes mainly through epigenetic mechanisms. In PCa, evidence accumulated that hundreds of lncRNAs are dysregulated. Functional analyses revealed their contribution to prostate carcinogenesis by targeting relevant pathways and gene regulation mechanisms including PTEN/AKT and androgen receptor signaling as well as chromatin remodeling complexes. Here we summarize our current knowledge on the roles of lncRNAs in PCa and their potential use as biomarkers for aggressive PCa and as novel therapeutic targets.

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