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 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 LINC01006 facilitates cell proliferation, migration and invasion in prostate cancer through targeting miR-34a-5p to up-regulate DAAM1

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Enhui Ma ◽  
Qianqian Wang ◽  
Jinhua Li ◽  
Xinqi Zhang ◽  
Zhenjia Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Gland ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Protein Coding ◽  
Novel Target

Abstract Background Prostate cancer (PCa) is a kind of malignancy occurring in the prostate gland. Substantial researches have proved the major role of long noncoding RNAs (lncRNAs) in PCa. However, the role of long intergenic non-protein coding RNA 1006 (LINC01006) in PCa has not been investigated yet. Methods RT-qPCR was used to examine the expression levels of LINC01006 and its downstream targets. The function of LINC01006 in PCa was tested by in vitro and in vivo assays. With application of RNA pull down, RNA immunoprecipitation (RIP) and luciferase reporter assays, the interaction among LINC01006, miR-34a-5p and disheveled associated activator of morphogenesis 1 (DAAM1) were verified. Results LINC01006 expression presented high in PCa cell lines. LINC01006 silencing suppressed cell proliferative, migratory, invasive capacities while accelerated apoptotic rate. Besides, LINC01006 knockdown also suppressed tumor growth and metastasis in vivo. Furthermore, miR-34a-5p, a tumor suppressor in PCa, was sponged by LINC01006. Moreover, DAAM1 was targeted by miR-34a-5p and promoted PCa progression. More intriguingly, rescue assays suggested that the inhibitory effect of LINC01006 knockdown on PCa development was offset by DAAM1 overexpression. Conclusions LINC01006 promoted PCa progression by sponging miR-34a-5p to up-regulate DAAM1, providing a novel target for PCa therapy.

Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies

2004 ◽  
Vol 108 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Ronan M. LONG ◽  
Colm MORRISSEY ◽  
John M. FITZPATRICK ◽  
R. William G. WATSON
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Prostate Gland ◽  
Western World ◽  
Cancer Therapies ◽  
Normal Prostate ◽  
Full Characterization ◽  
Prostate Epithelial Cells ◽  
Common Malignancy

Prostate cancer is the most common malignancy in males in the western world. However, little is known about its origin and development. This review highlights the biology of the normal prostate gland and the differentiation of basal epithelial cells to a secretory phenotype. Alterations in this differentiation process leading to cancer and androgen-independent disease are discussed, as well as a full characterization of prostate epithelial cells. A full understanding of the origin and characteristics of prostate cancer epithelial cells will be important if we are to develop therapeutic strategies to combat the heterogeneous nature of this disease.

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.

scholarly journals The role of Wnt5a in prostate gland development

2009 ◽  
Vol 328 (2) ◽  
pp. 188-199 ◽  
Author(s):  
Liwei Huang ◽  
Yongbing Pu ◽  
Wen Yang Hu ◽  
Lynn Birch ◽  
Douglas Luccio-Camelo ◽  
...  
Keyword(s):  
Prostate Gland ◽  
Gland Development

scholarly journals The role of inhibins and activins in prostate cancer pathogenesis.

2000 ◽  
pp. 243-256 ◽  
Author(s):  
C R Dowling ◽  
G P Risbridger
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Prostate Gland ◽  
Prostate Carcinogenesis ◽  
Cancer Pathogenesis ◽  
Number Of Patients ◽  
Related Proteins

Successful prostate cancer diagnosis and management continue to provide challenges for the clinician. While interventions aimed at the containment of both early and late disease continue to fail in a significant number of patients, the search for answers must incorporate an analysis of the processes of normal and aberrant growth and development within the gland itself. Inhibin and its structurally related protein, activin, are members of the transforming-growth-factor beta (TGFbeta) superfamily. Originally identified as regulators of FSH, these proteins are now recognised to have widespread biological functions. This might be expected of proteins that are structurally homologous to TGFbeta itself, which is recognised to have regulatory roles in both normal and malignant prostate tissue. The aim of this review is to examine the relationship between inhibins, activins and their related proteins and the development of prostate cancer. The homology with TGF, the pluripotent effects of activin on various tissues and the roles for inhibins in ovarian cancer make activins and inhibins candidate growth factors for involvement at multiple sites in the progression from benign disease to cancer. In compiling this review, we aim to delineate the changes in inhibins and activins in this pathway and in doing so implicate their potential roles in the progression of carcinogenesis. We will compare the changes in inhibin and its related proteins in prostate cancer to those that are known in ovarian cancer. We will discuss the similarities and differences between the putative role of activins and TGFbeta in prostate carcinogenesis. The importance of this review lies in demonstrating that inhibin, an endocrine hormone, and its related proteins may contribute to endocrine-related cancers, such as that of the prostate gland.

miR-1825 Accelerates Cell Proliferation and Inhibits Cell Apoptosis of Prostate Cancer via Targeting Suppressor of Cancer Cell Invasion

2021 ◽  
Vol 11 (5) ◽  
pp. 820-831
Author(s):  
Jun-Chao Bai ◽  
Guang-Yi Huang
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Cancer Cell Invasion ◽  
Normal Prostate

Prostate cancer (PC) is one major carcinoma threat to the health of males. microRNAs (miRNAs) are short non-coding transcripts with about 23 nt in length. Booming evidence has verified the various roles of miRNAs in human tumors. miR-1825 was once demonstrated to be highly expressed in PC, but the potential role of miR-1825 in PC has never been clarified yet. This work aimed to explore the function of miR-1825 and reveal the underlying modulation mechanism in PC. First, miR-1825 was detected to be elevated in PC cells compared with normal prostate cells, as proved by RT-qPCR. After miR-1825 expression was inhibited, cell proliferation was hindered and cell apoptosis was promoted, which was observed by CCK8, colony formation, TUNEL staining and western blot assays. Bioinformatics tools discovered the targeting of suppressor of cancer cell invasion (SCAI) by miR-1825, which was further confirmed by luciferase reporter assay. Then the suppression of miR-1825 on SCAI protein expression was verified by western blotting. Eventually, rescue assays were implemented and affirmed the miR-1825/SCAI axis in PC cells. In conclusion, our present research disclosed the oncogenic role of miR-1825 and the miR-1825/SCAI pathway in PC. These findings gave new clues for the therapy of PC.

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.

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