scholarly journals In touch with your feminine side: how oestrogen metabolism impacts prostate cancer

2016 ◽  
Vol 23 (6) ◽  
pp. R249-R266 ◽  
Author(s):  
Habibur P Rahman ◽  
Johannes Hofland ◽  
Paul A Foster
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Tumour Progression ◽  
Scientific Evidence ◽  
Prostate Gland ◽  
Incidence Rates ◽  
Prostate Tissue ◽  
Normal Prostate ◽  
Oestrogen Receptor Status ◽  
Molecular Action

Prostate cancer is the primary cancer in males, with increasing global incidence rates making this malignancy a significant healthcare burden. Androgens not only promote normal prostate maturity but also influence the development and progression of prostate cancer. Intriguingly, evidence now suggests endogenous and exogenous oestrogens, in the form of phytoestrogens, may be equally as relevant as androgens in prostate cancer growth. The prostate gland has the molecular mechanisms, catalysed by steroid sulphatase (STS), to unconjugate and utilise circulating oestrogens. Furthermore, prostate tissue also expresses enzymes essential for local oestrogen metabolism, including aromatase (CYP19A1) and 3β- and 17β-hydroxysteroid dehydrogenases. Increased expression of these enzymes in malignant prostate tissue compared with normal prostate indicates that oestrogen synthesis is favoured in malignancy and thus may influence tumour progression. In contrast to previous reviews, here we comprehensively explore the epidemiological and scientific evidence on how oestrogens impact prostate cancer, particularly focusing on pre-receptor oestrogen metabolism and subsequent molecular action. We analyse how molecular mechanisms and metabolic pathways involved in androgen and oestrogen synthesis intertwine to alter prostate tissue. Furthermore, we speculate on whether oestrogen receptor status in the prostate affects progression of this malignancy.

Magnetic resonance fingerprinting in prostate cancer before and after contrast enhancement

2021 ◽  
pp. 20210479
Author(s):  
Young Sub Lee ◽  
Moon Hyung Choi ◽  
Young Joon Lee ◽  
Dongyeob Han ◽  
Dong-Hyun Kim
Keyword(s):  
Prostate Cancer ◽  
Magnetic Resonance ◽  
Prostate Gland ◽  
Prostate Tissue ◽  
Normal Prostate ◽  
Adc Value ◽  
Contrast Enhanced ◽  
Normal Prostate Tissue ◽  
Adc Values ◽  
T1 And T2

Objectives: To assess the apparent diffusion coefficient (ADC) values and the T1 and T2 values derived from nonenhanced (NE) and contrast-enhanced (CE) magnetic resonance fingerprinting (MRF) in the prostate gland and to evaluate differences in values among prostate cancer, the normal peripheral zone (PZ) and the normal transition zone (TZ). Methods: Fifty-seven patients (median age, 73 years; range, 48–86) with prostate cancer who underwent multiparametric MRI including NE and CE MRF were included in this study. T1 and T2 values were extracted from NE and CE MRF, respectively. Five quantitative values (the ADC, NE T1, NE T2, CE T1 and CE T2 values) were measured in three areas: prostate cancer, PZ and TZ. We compared the values among the three areas and evaluated the differences between NE MRF and CE MRF values. Results: ADC values and MRF-derived values were significantly higher in PZ than prostate cancer or TZ (p < 0.001). TZ had a significantly lower CE T1 but significantly higher values of the other variables than prostate cancer (p < 0.001). The T1 values in all three areas and the T2 values in prostate cancer and TZ were significantly lower on CE MRF than on NE MRF (p < 0.001). Conclusions: Quantitative analysis of NE and CE MRI can be conducted by using the MRF technique. The ADC value and the T1 and T2 values from CE MRF and NE MRF were found to be significantly different between prostate cancer and normal prostate tissue. Advances in knowledge The T1 and T2 values from contrast-enhanced MR fingerprinting are significantly different between prostate cancer and normal prostate tissue.

scholarly journals DIETARY INTAKE OF MINERALS AND PROSTATE CANCER: INSIGHTS INTO PROBLEM BASED ON THE CHEMICAL ELEMENT CONTENTS IN THE PROSTATE GLAND

2015 ◽  
pp. 1-8
Author(s):  
V. Zaichick ◽  
S. Zaichick
Keyword(s):  
Prostate Cancer ◽  
Prostate Gland ◽  
Population Based ◽  
Prostate Tissue ◽  
Mineral Contents ◽  
Normal Prostate ◽  
Adult Men ◽  
Age Related ◽  
Mass Fractions ◽  
Normal Prostate Tissue

Objective: As men age total dietary mineral bioavailability falls which may increase the risk of prostate cancer. The aims of this study were to investigate the changes in main mineral contents in prostate gland that occurred with aging. Design: Population based study on changes in mineral contents in prostate gland with ageing. Participants and setting: 65 free-living healthy men aged 21-87 years who had died suddenly. Prostates were removed at necropsy and the samples of morphologic normal prostate tissue were investigated. Measurements: Contents of ten main minerals (B, Ca, Co, Cr, Cu, Fe, Mg, Mn, Se, and Zn) were determined by four instrumental analytical methods. Results: No any age-related deficiencies in minerals such as B, Ca, Co, Cr, Cu, Fe, Mg, Mn, Se, and Zn in the prostate tissue were found. Moreover, the mean mass fractions of Co, Fe, and Zn in prostate tissue for the age group adult men aged 41 years and older were statistically significant higher than for those younger than 40 years. Conclusions: Ageing is not associated with reduced mineral contents in prostate gland resulting in inadequate intakes in nutrients. Nutrition policy for men aged 41 years and older should include advice to decrease intakes of red meat for the purpose to reduce Fe and Zn intake.

scholarly journals Characterization of Proteins Regulated by Androgen and Protein Kinase a Signaling in VCaP Prostate Cancer Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1404
Author(s):  
Hye-Jin You ◽  
Byong-Chul You ◽  
Jong-Kwang Kim ◽  
Jae-Min Park ◽  
Bo-Seul Song ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Castration Resistant Prostate Cancer ◽  
Normal Prostate ◽  
Prostate Cancer Development ◽  
Kinase A

Androgen signaling via the androgen receptor (AR) is involved in normal prostate development and prostate cancer progression. In addition to androgen binding, a variety of protein kinases, including cyclic AMP-dependent protein kinase A (PKA), can activate the AR. Although hormone deprivation, especially that of androgen, continues to be an important strategy for treating prostate cancer patients, the disease ultimately progresses to castration-resistant prostate cancer (CRPC), despite a continuous hormone-deprived environment. To date, it remains unclear which pathways in this progression are active and targetable. Here, we performed a proteomic analysis of VCaP cells stimulated with androgen or forskolin to identify proteins specific for androgen-induced and androgen-bypassing signaling, respectively. Patterns of differentially expressed proteins were quantified, and eight proteins showing significant changes in expression were identified. Functional information, including a Gene Ontology analysis, revealed that most of these proteins are involved in metabolic processes and are associated with cancer. The mRNA and protein expression of selected proteins was validated, and functional correlations of identified proteins with signaling in VCaP cells were assessed by measuring metabolites related to each enzyme. These analyses offered new clues regarding effector molecules involved in prostate cancer development, insights that are supported by the demonstration of increased expression levels of the eight identified proteins in prostate cancer patients and assessments of the progression-free interval. Taken together, our findings show that aberrant levels of eight proteins reflect molecular changes that are significantly regulated by androgen and/or PKA signaling pathways, suggesting possible molecular mechanisms of CRPC.

scholarly journals The role of the androgen receptor as a driver and mitigator of cellular stress

2020 ◽  
Vol 65 (2) ◽  
pp. R19-R33
Author(s):  
Dimitrios Doultsinos ◽  
Ian Mills
Keyword(s):  
Prostate Cancer ◽  
Protein Synthesis ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Nuclear Hormone Receptor ◽  
Biological Processes ◽  
Normal Prostate ◽  
Mtor Activity

Prostate cancer is a high-incidence male cancer, which is dependent on the activity of a nuclear hormone receptor, the androgen receptor (AR). Since the AR is required for both normal prostate gland development and for prostate cancer progression, it is possible that prostate cancer evolves from perturbations in AR-dependent biological processes that sustain specialist glandular functions. The archetypal example of course is the use of prostate specific antigen (PSA), an organ-type specific component of the normal prostate secretome, as a biomarker of prostate cancer. Furthermore, localised prostate cancer is characterised by a low proliferative index and a heterogenous array of somatic mutations aligned to a multifocal disease pattern. We and others have identified a number of biological processes that are AR dependent and represent aberrations in significant glandular processes. Glands are characterised by high rates of metabolic activity including protein synthesis supported by co-dependent processes such as glycosylation, organelle biogenesis and vesicle trafficking. Impairments in anabolic metabolism and in protein folding/processing will inevitably impose proteotoxic and oxidative stress on glandular cells and, in particular, luminal epithelial cells for which secretion is their primary function. As cancer develops there is also significant metabolic dysregulation including impaired negative feedback effects on glycolytic and anabolic activity under conditions of hypoxia and heightened protein synthesis due to dysregulated PI 3-kinase/mTOR activity. In this review we will focus on the components of the AR regulome that support cancer development as well as glandular functions focussing on the unfolded protein response and on regulators of mTOR activity.

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 Increased Expressions of Matrix Metalloproteinases (MMPs) in Prostate Cancer Tissues of Men with Type 2 Diabetes

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 507
Author(s):  
Andras Franko ◽  
Lucia Berti ◽  
Jörg Hennenlotter ◽  
Steffen Rausch ◽  
Marcus O. Scharpf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Type 2 Diabetes ◽  
Matrix Metalloproteinases ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Prostate Tissue ◽  
Nuclear Antigen ◽  
Gene Expressions ◽  
Mesenchymal Transition

Type 2 diabetes (T2D) is associated with worse prognosis of prostate cancer (PCa). The molecular mechanisms behind this association are still not fully understood. The aim of this study was to identify key factors, which contribute to the more aggressive PCa phenotype in patients with concurrent T2D. Therefore, we investigated benign and PCa tissue of PCa patients with and without diabetes using real time qPCR. Compared to patients without diabetes, patients with T2D showed a decreased E-cadherin/N-cadherin (CDH1/CDH2) ratio in prostate tissue, indicating a switch of epithelial-mesenchymal transition (EMT), which is a pivotal process in carcinogenesis. In addition, the gene expression levels of matrix metalloproteinases (MMPs) and CC chemokine ligands (CCLs) were higher in prostate samples of T2D patients. Next, prostate adenocarcinoma PC3 cells were treated with increasing glucose concentrations to replicate hyperglycemia in vitro. In these cells, high glucose induced expressions of MMPs and CCLs, which showed significant positive associations with the proliferation marker proliferating cell nuclear antigen (PCNA). These results indicate that in prostate tissue of men with T2D, hyperglycemia may induce EMT, increase MMP and CCL gene expressions, which in turn activate invasion and inflammatory processes accelerating the progression of PCa.

The role of WNT10B in normal prostate gland development and prostate cancer

The Prostate ◽  
2019 ◽  
Vol 79 (14) ◽  
pp. 1692-1704 ◽  
Author(s):  
Ikenna Madueke ◽  
Wen‐Yang Hu ◽  
Danping Hu ◽  
Steven M. Swanson ◽  
Donald Vander Griend ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Gland ◽  
Normal Prostate ◽  
Gland Development

scholarly journals An expanded variant list and assembly annotation identifies multiple novel coding and noncoding genes for prostate cancer risk using a normal prostate tissue eQTL data set

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0214588
Author(s):  
Melissa S. DeRycke ◽  
Melissa C. Larson ◽  
Asha A. Nair ◽  
Shannon K. McDonnell ◽  
Amy J. French ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Prostate Tissue ◽  
Data Set ◽  
Normal Prostate ◽  
Normal Prostate Tissue ◽  
Eqtl Data
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