The role of SPARC in the TRAMP model of prostate carcinogenesis and progression

Background: Prostate cancer (PCa) represents a common disease in men aged >65 years. The role of physical activity (PA) in patients at risk or diagnosed with PCa represents an evolving issue. We aimed to summarize available evidences about the impact of PA on the pathophysiology and clinical outcomes of PCa. Methods: We performed a narrative review. Evidences about the role of PA in elderly patients in terms of PCa biology, epidemiology, oncological and functional outcomes, as well as in terms of impact on the outcomes of androgen deprivation therapy (ADT) were summarized. Results: Potential pathophysiological pathways hypothesized to explain the benefits of PA in terms of prostate carcinogenesis include circulating levels of Insulin-like growth factor-1 (IGF-1), oxidative stress, systemic inflammation, sex hormones, and myokines. Clinically, emerging evidences support the hypothesis that PA is associated with decreased PCa risk, improved PCa-related survival, improved functional outcomes, and reduced ADT-related adverse events.

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Abstract 535: The role of high mobility group box 1 (HMGB1) in prostate carcinogenesis

10.1158/1538-7445.am2012-535 ◽

2012 ◽

Cited By ~ 1

Author(s):

Purvi Patel ◽

Michelle Zheng ◽

Maarten C. Bosland ◽

André Kajdacsy-Balla ◽

Gnanasekar Munirathinam

Keyword(s):

High Mobility ◽

High Mobility Group ◽

Prostate Carcinogenesis

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Role of Estrogen in Androgen-Induced Prostate Carcinogenesis in NBL Rats

Hormones and Cancer ◽

10.1007/s12672-019-00360-7 ◽

2019 ◽

Vol 10 (2-3) ◽

pp. 77-88 ◽

Cited By ~ 4

Author(s):

Nur Ozten ◽

Katherine Vega ◽

Joachim Liehr ◽

Xi Huang ◽

Lori Horton ◽

...

Keyword(s):

Prostate Carcinogenesis

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ERβ and NFκB—Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells

Toxins ◽

10.3390/toxins12030199 ◽

2020 ◽

Vol 12 (3) ◽

pp. 199 ◽

Cited By ~ 2

Author(s):

Karolina Kowalska ◽

Dominika Ewa Habrowska-Górczyńska ◽

Kamila Domińska ◽

Kinga Anna Urbanek ◽

Agnieszka Wanda Piastowska-Ciesielska

Keyword(s):

Oxidative Stress ◽

Prostate Cancer ◽

Cancer Cells ◽

Prostate Cancer Cells ◽

M Cell ◽

Androgen Independence ◽

Prostate Carcinogenesis ◽

Cycle Arrest ◽

Light Chain Enhancer

Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) is commonly expressed in prostate cancer (PCa) cells and is associated with increased proliferation, metastases and androgen independence. Zearalenone (ZEA) is one of the most common mycotoxins contaminating food, which might mimic estrogens and bind to estrogen receptors (ERs). The ratio of androgens to estrogens in men decreases physiologically with age, and is believed to participate in prostate carcinogenesis. In this study, we evaluated the role of NFκB and ERβ in the induction of oxidative stress in human PCa cells by ZEA. As observed, ZEA at a dose of 30 µM induces oxidative stress in PCa cells associated with DNA damage and G2/M cell cycle arrest. We also observed that the inhibition of ERβ and NFΚB via specific inhibitors (PHTPP and BAY 117082) significantly increased ZEA-induced oxidative stress, although the mechanism seems to be different for androgen-dependent and androgen-independent cells. Based on our findings, it is possible that the activation of ERβ and NFΚB in PCa might protect cancer cells from ZEA-induced oxidative stress. We therefore shed new light on the mechanism of ZEA toxicity in human cells.

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Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells

Endocrine Related Cancer ◽

10.1677/erc.1.01043 ◽

2006 ◽

Vol 13 (1) ◽

pp. 151-167 ◽

Cited By ~ 83

Author(s):

Ta-Chun Yuan ◽

Suresh Veeramani ◽

Fen-Fen Lin ◽

Dmitry Kondrikou ◽

Stanislav Zelivianski ◽

...

Keyword(s):

Specific Antigen ◽

Neuron Specific Enolase ◽

Neuronal Morphology ◽

Receptor Protein ◽

Lncap Cells ◽

Normal Prostate ◽

Androgen Ablation ◽

Prostate Carcinogenesis ◽

Hormone Refractory

Neuroendocrine (NE) cells are the minor cell populations in normal prostate epithelial compartments. During prostate carcinogenesis, the number of NE cells in malignant lesions increases, correlating with its tumorigenicity and hormone-refractory growth. It is thus proposed that cancerous NE cells promote prostate cancer (PCa) cell progression and its androgen-independent proliferation, although the origin of the cancerous NE cells is not clear. To investigate the role of cancerous NE cells in prostate carcinogenesis, we characterized three NE subclone cell lines–NE-1.3, NE-1.8 and NE-1.9, which were transdifferentiated from androgen-sensitive human PCa LNCaP cells by culturing in an androgen-depleted environment, resembling clinical androgen-ablation therapy. These subclone cells acquire many features of NE cells seen in clinical prostate carcinomas, for example exhibiting a neuronal morphology and expressing multiple NE markers, including neuron-specific enolase, chromogranin B, neurotensin, parathyroid hormone-related peptide, and to a lesser degree for chromogranin A, while lacking androgen receptor (AR) or prostate specific antigen (PSA) expression. These cells represent terminally differentiated stable cells because after 3 months of re-culturing in a medium containing androgenic activity, they still retained the NE phenotype and expressed NE markers. Despite these NE cells having a slow growth rate, they readily developed xenograft tumors. Furthermore, media conditioned by these NE cells exhibited a stimulatory effect on proliferation and PSA secretion by LNCaP cells in androgen-deprived conditions. Additionally, we found that receptor protein tyrosine phosphatase α plays a role in upregulating multiple NE markers and acquiring the NE phenotype. These NE cells thus represent cancerous NE cells and could serve as a useful cell model system for investigating the role of cancerous NE cells in hormone-refractory proliferation of PCa cells.

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Androgen Receptor Signalling in Prostate Cancer: The Functional Consequences of Acetylation

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/862125 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 18

Author(s):

Derek N. Lavery ◽

Charlotte L. Bevan

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Progression ◽

Histone Deacetylases ◽

Transcriptional Response ◽

Fine Tuning ◽

Receptor Signalling ◽

Prostate Carcinogenesis ◽

Functional Consequences

The androgen receptor (AR) is a ligand activated transcription factor and member of the steroid hormone receptor (SHR) subfamily of nuclear receptors. In the early stages of prostate carcinogenesis, tumour growth is dependent on androgens, and AR directly mediates these effects by modulating gene expression. During transcriptional regulation, the AR recruits numerous cofactors with acetylation-modifying enzymatic activity, the best studied include p300/CBP and the p160/SRC family of coactivators. It is known that recruitment of histone acetyltransferases (HATs) and histone deacetylases (HDACs) is key in fine-tuning responses to androgens and is thus likely to play a role in prostate cancer progression. Further, these proteins can also modify the AR itself. The functional consequences of AR acetylation, the role of modifying enzymes in relation to AR transcriptional response, and prostate cancer will be discussed.

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The role of inhibins and activins in prostate cancer pathogenesis.

Endocrine Related Cancer ◽

10.1677/erc.0.0070243 ◽

2000 ◽

pp. 243-256 ◽

Cited By ~ 24

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.

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