scholarly journals Differential expression of steroid 5α-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

2010 ◽  
Vol 17 (3) ◽  
pp. 757-770 ◽  
Author(s):  
Kakoli Das ◽  
Pia D N Lorena ◽  
Lai Kuan Ng ◽  
Diana Lim ◽  
Liang Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Specific Antigen ◽  
Biological Role ◽  
Prostate Cell ◽  
Cellular Expression ◽  
Significant Difference ◽  
Angiogenic Genes ◽  
Angiogenesis Pathway

The biological role of steroid 5α-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor β 1 (TGFB1), endothelin (EDN1), TGFα (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 μM). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors.

scholarly journals Growth factors in benign prostatic hyperplasia (BPH) and prostate carcinoma

1995 ◽  
Vol 62 (4) ◽  
pp. 509-517
Author(s):  
F. Di Silverio ◽  
G. D'Eramo ◽  
A. Sciarra ◽  
M. Buscarini ◽  
P. Casale ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Steroid Receptors ◽  
Cancer Cell Line ◽  
Trophic Factors ◽  
Cancer Tissue ◽  
Target Tissue ◽  
Prostate Cell

It has been stated that, although steroid hormones are a necessary prerequisiste for prostate cell proliferation, cell division is not an inevitable consequence of the presence of hormones. The possibility that diffusible trophic factors play an important role in the normal and pathologic regulatory process within the prostate, offers a new and exciting research initiative. In order to better clarify the relationships between Epidermal growth factor (EGF), its receptor (EGFr) and steroid receptors at target tissue levels, we have demonstrated a statistically significant linear correlation between irEGF and nuclear androgen receptor (nAR) levels in human BPH tissue. Moreover we started an investigation to analyse the stroma-epithelium ratio and to verify EGF, EGFr, AR, DHT concentrations in the periurethral, central and peripheral zone of human BPH tissue. In all BPH zones the quantitative method of image analysis showed a higher percentage content of stroma than of epithelium. The highest levels of EGF, DHT and stroma content were present in the periurethral zone, where BPH begins. Both androgen and antiandrogen treatment enhance the proliferation rate of prostate cancer cell line LNCaP. After prolonged R1881 administration, a marked increase of EGF release was observed, completely blocked by the addition of OH-flutamide. The role of Transforming growth factor beta 1 (TGF beta1) in prostate cancer has been also demonstrated in prostate cancer tissue of patients submitted to radical prostatectomy.

Expression of transforming growth factor-beta 1 in prostate cancer.

Endocrinology ◽  
1994 ◽  
Vol 135 (5) ◽  
pp. 2240-2247 ◽  
Author(s):  
M S Steiner ◽  
Z Z Zhou ◽  
D C Tonb ◽  
E R Barrack
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

Role of transforming growth factor-?1 in prostate cancer

2001 ◽  
Vol 52 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Pernilla Wikstr�m ◽  
Jan-Erik Damber ◽  
Anders Bergh
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor

scholarly journals Recruitment of β-Catenin by Wild-Type or Mutant Androgen Receptors Correlates with Ligand-Stimulated Growth of Prostate Cancer Cells

2004 ◽  
Vol 18 (10) ◽  
pp. 2388-2401 ◽  
Author(s):  
David Masiello ◽  
Shao-Yong Chen ◽  
Youyuan Xu ◽  
Manon C. Verhoeven ◽  
Eunis Choi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Nuclear Receptor ◽  
Specific Antigen ◽  
Prostate Cancer Cells ◽  
Prostate Cell ◽  
Nuclear Receptor Corepressor ◽  
Prostate Cancers

Abstract Prostate cancers respond to treatments that suppress androgen receptor (AR) function, with bicalutamide, flutamide, and cyproterone acetate (CPA) being AR antagonists in clinical use. As CPA has substantial agonist activity, it was examined to identify AR coactivator/corepressor interactions that may mediate androgen-stimulated prostate cancer growth. The CPA-liganded AR was coactivated by steroid receptor coactivator-1 (SRC-1) but did not mediate N-C terminal interactions or recruit β-catenin, indicating a nonagonist conformation. Nonetheless, CPA did not enhance AR interaction with nuclear receptor corepressor, whereas the AR antagonist RU486 (mifepristone) strongly stimulated AR-nuclear receptor corepressor binding. The role of coactivators was further assessed with a T877A AR mutation, found in LNCaP prostate cancer cells, which converts hydroxyflutamide (HF, the active flutamide metabolite) into an agonist that stimulates LNCaP cell growth. The HF and CPA-liganded T877A ARs were coactivated by SRC-1, but only the HF-liganded T877A AR was coactivated by β-catenin. L-39, a novel AR antagonist that transcriptionally activates the T877A AR, but still inhibits LNCaP growth, similarly mediated recruitment of SRC-1 and not β-catenin. In contrast, β-catenin coactivated a bicalutamide-responsive mutant AR (W741C) isolated from a bicalutamide-stimulated LNCaP subline, further implicating β-catenin recruitment in AR-stimulated growth. Androgen-stimulated prostate-specific antigen gene expression in LNCaP cells could be modulated by β-catenin, and endogenous c-myc expression was repressed by dihydrotestosterone, but not CPA. These results indicate that interactions between AR and β-catenin contribute to prostate cell growth in vivo, although specific growth promoting genes positively regulated by AR recruitment of β-catenin remain to be identified.

The Current Role of Immunotherapy in mCRPC: A Systematic Review

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Dalibey H ◽  
◽  
Hansen TF ◽  
Zedan AH ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Treatment Modalities ◽  
Significant Difference

Background: The development of immunotherapy has shown promising results in several malignant diseases, including prostate cancer, calling for a systematic review of the current literature. This review aims to evaluate the present data and prospects of immune checkpoint inhibitors in metastatic Castration Resistant Prostate Cancer (mCRPC). Methods: Articles were identified via a systematic search of the electronic database Pubmed, in accordance with the PICO process and following the PRISMA guidelines. Articles in English studying immune checkpoint inhibitors in patients with mCRPC published between March 2010 and March 2020 were eligible for inclusion. Endpoints of interest were Overall Survival (OS), Progression-Free Survival (PFS), clinical Overall Response Rate (ORR), and Prostate-Specific Antigen (PSA) response rate. Results: Ten articles were identified as eligible for inclusion. The studies primarily explored the use of Ipilimumab, a CTLA-4 inhibitor, and Pembrolizumab, a PD-1 inhibitor. These drugs were both used either as monotherapy or in combination with other treatment modalities. The largest trial included in the review demonstrated no significant difference in overall survival between the intervention and placebo. However, two studies presented promising data combing immunotherapy and immune vaccines. Grade 3 and 4 adverse events ranging from 10.1% to 82.3%, whit diarrhea, rash, and fatigue were the most frequently reported. Forty relevant ongoing trials were identified exploring immunotherapy with or without a parallel treatment modality. Conclusion: Overall, the current data shows that the effect of immune checkpoint inhibitors as monotherapy may have limited impact on mCRPC, and the results from ongoing combinational trials are eagerly awaited.

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