scholarly journals Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells

2021 ◽  
Vol 22 (21) ◽  
pp. 12040
Author(s):  
Lenny K. Hong ◽  
Shrinidhi Kadkol ◽  
Maria Sverdlov ◽  
Irida Kastrati ◽  
Mostafa Elhodaky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
African American Men ◽  
Soft Agar ◽  
Cancer Tissue ◽  
Prostate Epithelial Cells ◽  
Increased Risk ◽  
Caucasian Men

SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3′-untranslated (3′-UTR) region of the SELENOF mRNA. Polymorphisms in the 3′-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions. Using a prostate cancer tissue microarray, it was previously established that the reduction of SELENOF in the cancers from African American men was significantly greater than in cancers from Caucasian men. When SELENOF levels in human prostate immortalized epithelial cells were reduced with an shRNA construct, those cells acquired the ability to grow in soft agar, increased the ability to migrate in a scratch assay and acquired features of energy metabolism associated with prostate cancer. These results support a role of SELENOF loss in prostate cancer progression and further indicate that SELENOF loss and genotype may contribute to the disparity in prostate cancer mortality experienced by African American men.

scholarly journals Reducing Selenoprotein F Promotes the Transformation of Immortalized Prostate Epithelial Cells

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1809-1809
Author(s):  
Lenny Hong ◽  
Mostafa Elhodaky ◽  
Shrinidhi Kadkol ◽  
Alan Diamond
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
Tca Cycle ◽  
Soft Agar ◽  
Metabolic Shift ◽  
Normal Prostate ◽  
Funding Sources ◽  
Prostate Cells ◽  
Prostate Epithelial Cells

Abstract Objectives Selenoprotein F (SELENOF) levels are responsive to available dietary selenium and found in high levels in benign prostate cells. It is implicated in prostate cancer (PCa) mortality due to associations between polymorphisms in the corresponding gene and death from the disease. SELENOF levels are dramatically lower in prostate cancer compared to adjacent benign tissue. The objective of this study was to determine whether reducing SELENOF levels in human, non-transformed RWPE-1 prostate epithelial cells alters their phenotype to implicate SELENOF loss in PCa progression. Methods SELENOF levels were reduced in RWPE-1 cells that express high levels of SELENOF using a SELENOF shRNA construct. Proliferation was determined by quantifying DNA using fluorometric dsDNA quantitation. Growth in soft agar and cell mobility of cells in culture (wound healing assay) were imaged using an Evos FL microscope and quantified using Image J software. The oxygen consumption rate (OCR) was measured using a Seahorse XFe24 Analyzer. Results SELENOF levels were reduced in RWPE-1 and these cells exhibited decreased contact inhibition in culture (n = 3, P < 0.001) when compared to controls. Normal prostate epithelial cells are atypical in that they rely on glycolysis for energy production, have a truncated TCA cycle, and a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) occurs in PCa. Reducing SELENOF in RWPE-1 cells resulted in higher OCR compared to controls, indicating that SELENOF can impact the sources and pathways used in cellular energy metabolism. Conclusions Reduced SELENOF levels in RWPE-1 prostate cells resulted in properties consistent with a transformed phenotype and an increase in OCR, and indicating that the reduction in SELENOF may contribute a metabolic shift towards a PCa cancer-like metabolism. Together, these results indicate that SELENOF loss likely contributes to cancer progression. Funding Sources This work was supported by a grant from the Department of Defense to AMD and a Pre-Doctoral Education for Clinical and Translational Scientists Fellowship to LKH.

scholarly journals GPX1 Localizes to the Nucleus in Prostate Epithelium and its Levels are not Associated with Prostate Cancer Recurrence

Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 167 ◽  
Author(s):  
Dede Ekoue ◽  
Emmanuel Ansong ◽  
Lenny Hong ◽  
Larisa Nonn ◽  
Virgilia Macias ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Prostate Cancer Risk ◽  
Cancer Recurrence ◽  
Lipid Peroxides ◽  
Cancer Tissue ◽  
Nuclear Staining ◽  
Dietary Intakes ◽  
Prostate Epithelial Cells ◽  
Prostate Cancer Recurrence

Glutathione peroxidase 1 (GPX1) is an extensively studied selenium-dependent protein that reduces hydrogen and lipid peroxides to water. Because of its antioxidant function and its responsiveness to dietary intakes of selenium, an essential trace element whose levels are inversely associated with prostate cancer risk, GPX1 levels were assessed in a prostate cancer tissue microarray, comparing cases of recurrent prostate cancer following prostatectomy to non-recurrent controls. While GPX1 is generally considered as a protein that resides in both the cytoplasm and mitochondria, we detected strong nuclear staining by immunofluorescence using GPX1-specific antibodies. Nuclear localization of GPX1 was also observed in both primary prostate epithelial cells and the immortalized prostate-derived cell line RWPE-1, but not in LNCaP or PC3 prostate tumor-derived cell lines. Quantification of GPX1 levels in the entire cell, the cytoplasm, and the nucleus did not indicate any association of either its levels or subcellular distribution with prostate cancer recurrence. While GPX1 levels may not have an impact on survival among men with prostate cancer, the data indicates that this extensively characterized protein may have a novel function in the nucleus of prostate epithelial cells.

Elevation of Stromal-Derived Mediators of Inflammation Promote Prostate Cancer Progression in African-American Men

2018 ◽  
Vol 78 (21) ◽  
pp. 6134-6145 ◽  
Author(s):  
Marc Gillard ◽  
Rodrigo Javier ◽  
Yuan Ji ◽  
S. Lilly Zheng ◽  
Jianfeng Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Cancer Progression ◽  
African American Men ◽  
Prostate Cancer Progression ◽  
Mediators Of Inflammation

scholarly journals Cultural Adaptation of Evidence-Based Lifestyle Interventions for African American Men With Prostate Cancer: A Dyadic Approach

2020 ◽  
Vol 14 (6) ◽  
pp. 155798832094544
Author(s):  
Dalnim Cho ◽  
Karen Basen-Engquist ◽  
Chiara Acquati ◽  
Curtis Pettaway ◽  
Hilary Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Cancer Survivors ◽  
Lifestyle Intervention ◽  
Cancer Progression ◽  
Healthy Lifestyle ◽  
African American Men ◽  
Evidence Based ◽  
Lifestyle Interventions ◽  
Intervention Adaptation

Although a number of lifestyle interventions have been developed for cancer survivors, the extent to which they are effective for African American men with cancer is unclear. Given that African American men have the highest prostate cancer burden and the lack of proven interventions, this study developed a culturally-tailored lifestyle intervention for African American men with prostate cancer and their partners that aimed to improve healthy lifestyle behaviors (physical activity and healthy eating) and quality of life. The aim of the present study is to provide a detailed overview of the model-based process of intervention adaptation. Based on the IM Adapt approach (Highfield et al., 2015) and Typology of Adaptation (Davidson et al., 2013), the present study adapted existing, evidence-based interventions to address African American prostate cancer survivors’ and their partners’ potential unmet needs including anxiety/uncertainty about cancer progression, communication between partners, cultural sensitivity, and concordance/discordance of motivation and behaviors between partners. The intervention adaptation was a comprehensive and fluid process. To the best knowledge of the author, this is the first couple-based lifestyle intervention specifically developed for African American men with prostate cancer. The present study will be highly informative to future investigators by providing flexible and detailed information regarding lifestyle intervention adaptation for racial/ethnic minority men with prostate cancer and their partners.

ELEVATED SERUM LOW DENSITY LIPOPROTEIN (LDL) IS ASSOCIATED WITH AN INCREASED RISK OF PROSTATE CANCER IN AFRICAN-AMERICAN MEN

2008 ◽  
Vol 179 (4S) ◽  
pp. 150-150
Author(s):  
Kelvin A Moses ◽  
Thura T Abd ◽  
John A Hall ◽  
Michael Goodman ◽  
Muta M Issa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African American Men ◽  
Low Density Lipoprotein ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Low Density ◽  
Increased Risk

scholarly journals African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men

2015 ◽  
Vol 33 (2) ◽  
pp. 70.e15-70.e22 ◽  
Author(s):  
Kosj Yamoah ◽  
Curtiland Deville ◽  
Neha Vapiwala ◽  
Elaine Spangler ◽  
Charnita M. Zeigler-Johnson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African American Men ◽  
Disease Recurrence ◽  
Low Grade ◽  
Caucasian Men

Risk of more advanced cancer at surgery in African American men eligible for active surveillance.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15214-e15214
Author(s):  
Amirali H Salmasi ◽  
Misop Han ◽  
Isaac Yi Kim
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Advanced Cancer ◽  
Active Surveillance ◽  
African American Men ◽  
Low Grade ◽  
Inclusion Criteria ◽  
Medical Institutions ◽  
Caucasian Men ◽  
Preoperative Predictors

e15214 Background: African-American (AA) men have a higher risk for developing prostate cancer (PCa) and dying of PCa compared to Caucasian men. Active surveillance (AS) is an acceptable management for males with low volume and low grade PCa. In Caucasian men who were eligible for AS, the risk of non-organ-confined disease [NOC] at radical prostatectomy (RP) ranges between 7.8 and 10.9% (Kang et al 2011, Mufarrij et al 2010). It is unclear whether AA men with favorable risk PCa can undergo AS safely. We evaluated changes in staging and grading of PCa in a cohort of AA males that met the criteria for AS but underwent RP. Methods: Between 1997 and 2011, 1536 AA men underwent RP at either Johns Hopkins Medical Institutions or Cancer Institute of New Jersey. Pathological characteristics of patients who fulfilled the inclusion criteria under the National Cancer Institute (NCI) AS criteria were examined. NOC (ECE/SV+/LN+) and upgrading (Gleason <7 in biopsy to Gleason >6 in RP) was evaluated. We tried to identify preoperative predictors of more advanced cancer (NOC and/or upgrading). Results: We identified 212 men who underwent RP, eligible for AS based on NCI criteria. Among 212 men, 92 (37.7%) men showed NOC and/or upgrading, defined SV involvement in 5 (2.4%), ECE in 53 (25%), and increased Gleason (<7 to >6) in 69 (32%) men. Pre-operative PSA level (OR 1.2, p < 0.05) and age (OR 1.06, p < 0.01) were significantly associated with more advanced cancer. No significant association was found between BMI, tissue percentage, or positive cores with more advanced cancer. Conclusions: AS in AA with prostate cancer carries higher risk of NOC compared to non-AA population. More stringent AS entrance criteria may be necessary for AA men.

scholarly journals Prostate Cancer Screening in African American Men: Barriers and Methods for Improvement

2008 ◽  
Vol 2 (2) ◽  
pp. 172-177 ◽  
Author(s):  
Diane Reynolds
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Cancer Screening ◽  
Access To Health Care ◽  
African American Men ◽  
Prostate Cancer Screening ◽  
Medical Profession ◽  
Inadequate Knowledge ◽  
Incidence And Mortality ◽  
Caucasian Men

African American men have the highest rate of incidence for prostate cancer in the world and are more likely to die from the disease than other ethnic groups (National Institutes of Health, 1996). Routine screening for prostate cancer can lead to early detection of the disease, thereby reducing negative outcomes, but studies have shown that African American men are less likely than Caucasian men to engage in screening practices. Lack of access to health care, socioeconomic status, inadequate knowledge, fear, patient-provider communication, distrust of the medical profession, and aversion to digital rectal exam have been identified as possible barriers to prostate cancer screening in African American men. This literature review explores causes of this striking disparity between prostate cancer incidence and mortality in African American men and cites strategies used to improve prostate cancer screening rates among this population.

Sign in / Sign up

Export Citation Format

Share Document