scholarly journals Epigenetics in Prostate Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Costantine Albany ◽  
Ajjai S. Alva ◽  
Ana M. Aparicio ◽  
Rakesh Singal ◽  
Sarvari Yellapragada ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Histone Modification ◽  
Dna Sequences ◽  
Gene Function ◽  
Histone Deacetylases ◽  
Gene Promoter ◽  
The United States ◽  
Dna Hypermethylation ◽  
Promoter Regions ◽  
Prostate Cells

Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

scholarly journals GSTP1 positive prostatic adenocarcinomas are more common in Black than White men in the United States

2020 ◽  
Author(s):  
Igor Vidal ◽  
Qizhi Zheng ◽  
Jessica L. Hicks ◽  
Jiayu Chen ◽  
Elizabeth A. Platz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Black Men ◽  
Cpg Island ◽  
Molecular Subtype ◽  
White Men ◽  
The United States ◽  
Dna Hypermethylation ◽  
Black Patients ◽  
Prostate Cancers ◽  
White Patients

GSTP1 is a member of the Glutathione-S-transferase (GSTS) family silenced by CpG island DNA hypermethylation in 90-95% of prostate cancers. However, prostate cancers expressing GSTP1 have not been well characterized. We used immunohistochemistry against GSTP1 to examine 1673 primary prostatic adenocarcinomas on TMAs with redundant sampling from the index tumor from prostatectomies. GSTP1 protein was positive in at least one TMA core in 7.7% of cases and in all TMA cores in 4.4% of cases. The percentage of adenocarcinomas from Black patients who had any GSTP1 positive TMA cores was 14.9%, which was 2.5 times higher than the percentage from White patients (5.9%; P < 0.001). Further, the percentages of tumors from Black patients who had all TMA spots positive for GSTP1 (9.5%) was 3-fold higher than the percentage from White patients (3.2%; P<0.001). The increased percentage of GSTP1 positive cases in Black men was present only in ERG positive cases. By in situ hybridization, GSTP1 mRNA expression was concordant with protein staining, supporting the lack of silencing of at least some GSTP1 alleles in GSTP1-positive tumor cells. This is the first report revealing that the GSTP1-positive prostate cancer subset is substantially over-represented among prostate cancers from Black compared to White men. This observation should prompt additional studies to determine whether GSTP1 positive cases represent a distinct molecular subtype of prostate cancer and whether GSTP1 expression could provide a biological underpinning for the observed disparate outcomes for Black men.

132: Association of MMP-1 Gene Promoter Polymorphism with the Risk of Prostate Cancer and MMP-1 Expression in Radical Prostatectomy Specimens

2006 ◽  
Vol 175 (4S) ◽  
pp. 42-42
Author(s):  
Norihiko Tsuchiya ◽  
Shintaro Narita ◽  
Teruaki Kumazawa ◽  
Yohei Horikawa ◽  
Hideaki Kakinuma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Gene Promoter ◽  
Promoter Polymorphism ◽  
Gene Promoter Polymorphism

Denaturing High Performance Liquid Chromatography and Bioinformatics - Two Modern Tools for Extracellular Superoxide Dismutase (SOD3) Gene Promoter Analysis

2008 ◽  
Vol 59 (7) ◽  
Author(s):  
Corina Samoila ◽  
Alfa Xenia Lupea ◽  
Andrei Anghel ◽  
Marilena Motoc ◽  
Gabriela Otiman ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Transcription Factors ◽  
Liquid Chromatography ◽  
Dna Sequences ◽  
High Performance ◽  
Zinc Finger Protein ◽  
High Capacity ◽  
Gene Promoter ◽  
Experimental Approaches ◽  
Myeloid Zinc Finger

Denaturing High Performance Liquid Chromatography (DHPLC) is a relatively new method used for screening DNA sequences, characterized by high capacity to detect mutations/polymorphisms. This study is focused on the Transgenomic WAVETM DNA Fragment Analysis (based on DHPLC separation method) of a 485 bp fragment from human EC-SOD gene promoter in order to detect single nucleotide polymorphism (SNPs) associated with atherosclerosis and risk factors of cardiovascular disease. The fragment of interest was amplified by PCR reaction and analyzed by DHPLC in 100 healthy subjects and 70 patients characterized by atheroma. No different melting profiles were detected for the analyzed DNA samples. A combination of computational methods was used to predict putative transcription factors in the fragment of interest. Several putative transcription factors binding sites from the Ets-1 oncogene family: ETS member Elk-1, polyomavirus enhancer activator-3 (PEA3), protein C-Ets-1 (Ets-1), GABP: GA binding protein (GABP), Spi-1 and Spi-B/PU.1 related transcription factors, from the Krueppel-like family: Gut-enriched Krueppel-like factor (GKLF), Erythroid Krueppel-like factor (EKLF), Basic Krueppel-like factor (BKLF), GC box and myeloid zinc finger protein MZF-1 were identified in the evolutionary conserved regions. The bioinformatics results need to be investigated further in others studies by experimental approaches.

scholarly journals CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression

2019 ◽  
Vol 12 (2) ◽  
pp. 89
Author(s):  
Janeen H. Trembley ◽  
Betsy T. Kren ◽  
Md. J. Abedin ◽  
Daniel P. Shaughnessy ◽  
Yingming Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Inhibitory Effect ◽  
Strongly Correlated ◽  
Protein Levels ◽  
Small Molecule Inhibition ◽  
Prostate Cells ◽  
Cell Death Response ◽  
Stress Signals ◽  
Castrate Resistant

The prosurvival protein kinase CK2, androgen receptor (AR), and nuclear factor kappa B (NFκB) interact in the function of prostate cells, and there is evidence of crosstalk between these signals in the pathobiology of prostate cancer (PCa). As CK2 is elevated in PCa, and AR and NFκB are involved in the development and progression of prostate cancer, we investigated their interaction in benign and malignant prostate cells in the presence of altered CK2 expression. Our results show that elevation of CK2 levels caused increased levels of AR and NFκB p65 in prostate cells of different phenotypes. Analysis of TCGA PCa data indicated that AR and CK2α RNA expression are strongly correlated. Small molecule inhibition or molecular down-regulation of CK2 caused reduction in AR mRNA expression and protein levels in PCa cells and in orthotopic xenograft tumors by various pathways. Among these, regulation of AR protein stability plays a unifying role in CK2 maintenance of AR protein levels. Our results show induction of various endoplasmic reticulum stress signals after CK2 inhibition, which may play a role in the PCa cell death response. Of note, CK2 inhibition caused loss of cell viability in both parental and enzalutamide-resistant castrate-resistant PCa cells. The present work elucidates the specific link of CK2 to the pathogenesis of PCa in association with AR and NFκB expression; further, the observation that inhibition of CK2 can exert a growth inhibitory effect on therapy-resistant PCa cells emphasizes the potential utility of CK2 inhibition in patients who are on enzalutamide treatment for advanced cancer.

scholarly journals Distinct roles for the RNA-binding protein Staufen1 in prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristen A. Marcellus ◽  
Tara E. Crawford Parks ◽  
Shekoufeh Almasi ◽  
Bernard J. Jasmin
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Rna Binding ◽  
Prostate Cancer Cell ◽  
Rna Binding Protein ◽  
Migration And Invasion ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Prostate Cells

Abstract Background Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. Methods Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. Results We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. Conclusions Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.

scholarly journals Metastatic Prostate Cancer Involving the Sphenoid Sinus and Mandible

2021 ◽  
pp. 014556132110060
Author(s):  
Fadlullah Ba’th ◽  
Tanisha Hutchinson ◽  
Annie Meares ◽  
David Hamlar
Keyword(s):  
Prostate Cancer ◽  
Sphenoid Sinus ◽  
Metastatic Prostate Cancer ◽  
The United States ◽  
Endoscopic Examination ◽  
Atypical Presentation ◽  
Rare Presentation ◽  
The Third ◽  
Pathological Evaluation ◽  
Low Threshold

Prostate cancer is the third most leading cause of cancer in men in the United States. Although expected metastatic spread to bone, liver, and lymph nodes are often monitored, there are other rare presentations that can occur. This case report demonstrates a rare presentation of prostate cancer spreading to the paranasal sinuses and orbit. Not only did this case have an atypical presentation mimicking infection, the diagnosis was also only achieved through pathological evaluation after an endoscopic examination and biopsy. This case demonstrates the importance of a low threshold for endoscopic examinations in uncertain sinonasal presentations, and consistent biopsies when performing endoscopic examinations.

scholarly journals A Synthetic Biology Approach Using Engineered Bacteria to Detect Perfluoroalkyl Substance (PFAS) Contamination in Water

2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 801-807
Author(s):  
Nathaniel A Young ◽  
Ryan L Lambert ◽  
Angela M Buch ◽  
Christen L Dahl ◽  
Jackson D Harris ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Dna Sequences ◽  
Detection System ◽  
The United States ◽  
Detection Methods ◽  
Health Concern ◽  
Contaminated Water ◽  
Engineered Bacteria ◽  
Synthetic Biology Approach ◽  
Rhodococcus Jostii

ABSTRACT Introduction Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds used industrially for a wide variety of applications. These PFAS compounds are very stable and persist in the environment. The PFAS contamination is a growing health issue as these compounds have been reported to impact human health and have been detected in both domestic and global water sources. Contaminated water found on military bases poses a potentially serious health concern for active duty military, their families, and the surrounding communities. Previous detection methods for PFAS in contaminated water samples require expensive and time-consuming testing protocols that limit the ability to detect this important global pollutant. The main objective of this work was to develop a novel detection system that utilizes a biological reporter and engineered bacteria as a way to rapidly and efficiently detect PFAS contamination. Materials and Methods The United States Air Force Academy International Genetically Engineered Machine team is genetically engineering Rhodococcus jostii strain RHA1 to contain novel DNA sequences composed of a propane 2-monooxygenase alpha (prmA) promoter and monomeric red fluorescent protein (mRFP). The prmA promoter is activated in the presence of PFAS and transcribes the mRFP reporter. Results The recombinant R. jostii containing the prmA promoter and mRFP reporter respond to exposure of PFAS by activating gene expression of the mRFP. At 100 µM of perfluorooctanoic acid, the mRFP expression was increased 3-fold (qRT-PCR). Rhodococcus jostii without exposure to PFAS compounds had no mRFP expression. Conclusions This novel detection system represents a synthetic biology approach to more efficiently detect PFAS in contaminated samples. With further refinement and modifications, a similar system could be readily deployed in the field around the world to detect this critical pollutant.

scholarly journals Cutaneous Metastasis of Prostate Adenocarcinoma: A Rare Presentation of a Common Disease

2021 ◽  
Vol 9 ◽  
pp. 232470962199076
Author(s):  
Alexander Dills ◽  
Okechukwu Obi ◽  
Kevin Bustos ◽  
Jesse Jiang ◽  
Shweta Gupta
Keyword(s):  
Prostate Cancer ◽  
Serine Proteases ◽  
Cancer Genetics ◽  
Performance Status ◽  
Distant Metastases ◽  
The United States ◽  
Cutaneous Metastasis ◽  
Common Disease ◽  
Cutaneous Metastases ◽  
Rare Presentation

Prostate cancer is the most common cancer affecting men in the United States and the second greatest cause of cancer-related death. Metastases usually occur to bone followed by distant lymph nodes and then viscera. Cutaneous metastases are extremely rare. Their presence indicates advanced disease and a poor prognosis. As they are highly variable in appearance and may mimic a more benign process, biopsy is essential for identification. Serine proteases, particularly human tissue kallikreins, may play an important role in promoting metastasis and facilitate infiltration of the skin. Individual cancer genetics may predispose to more aggressive cancer and thus earlier and more distant metastases. In this article, we report our case of a 67-year-old man with a 4-year history of castrate-resistant prostate cancer with cutaneous metastases confirmed by histology. Despite multiple lines of systemic therapy, the patient suffered progressive disease with worsening performance status and was enrolled in hospice.

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