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Pten and prostate

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https://www.readbyqxmd.com/read/29330357/knockdown-of-phospholipase-c%C3%AE%C2%B5-plc%C3%AE%C2%B5-inhibits-cell-proliferation-via-phosphatase-and-tensin-homolog-deleted-on-chromosome-10-pten-akt-signaling-pathway-in-human-prostate-cancer
#1
Xiao Wang, Yanru Fan, Zhongbo Du, Jiaxin Fan, Yanni Hao, Jinhua Wang, Xiaohou Wu, Chunli Luo
BACKGROUND Phospholipase Cε (PLCε), a member of the plc family, has been extensively studied to reveal its role in the regulation of different cell functions, but understanding of the underlying mechanisms remains limited. In the present study, we explored the effects of PLCε on PTEN (phosphatase and tensin homolog deleted on chromosome 10) in cell proliferation in prostate cancer cells. MATERIAL AND METHODS We assessed PLCε and PTEN expression in human benign prostate tissues compared to prostate cancer tissues by immunohistochemistry...
January 13, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29304771/high-bcar1-expression-is-associated-with-early-psa-recurrence-in-erg-negative-prostate-cancer
#2
Asmus Heumann, Nina Heinemann, Claudia Hube-Magg, Dagmar S Lang, Katharina Grupp, Martina Kluth, Sarah Minner, Christina Möller-Koop, Markus Graefen, Hans Heinzer, Maria Christina Tsourlakis, Waldemar Wilczak, Corinna Wittmer, Frank Jacobsen, Hartwig Huland, Ronald Simon, Thorsten Schlomm, Guido Sauter, Stefan Steurer, Patrick Lebok, Andrea Hinsch
BACKGROUND: Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. METHODS: To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples. BCAR1 expression levels were compared with clinical characteristics, PSA recurrence, molecular subtype defined by ERG status and 3p, 5q, 6q and PTEN deletion. RESULTS: BCAR1 staining was barely detectable in normal prostate glands but seen in 77...
January 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29302046/p53-status-in-the-primary-tumor-predicts-efficacy-of-subsequent-abiraterone-and-enzalutamide-in-castration-resistant-prostate-cancer
#3
Benjamin L Maughan, Liana B Guedes, Kenneth Boucher, Gaurav Rajoria, Zach Liu, Szczepan Klimek, Roberto Zoino, Emmanuel S Antonarakis, Tamara L Lotan
BACKGROUND: We tested whether tissue-based analysis of p53 and PTEN genomic status in primary tumors is predictive for subsequent sensitivity to abiraterone and enzalutamide in castration-resistant prostate cancer (CRPC). METHODS: We performed a retrospective analysis of 309 consecutive patients with CRPC treated with abiraterone or enzalutamide. Of these, 101 men (33%) had available primary tumor tissue for analysis. We screened for deleterious TP53 missense mutations and PTEN deletions using genetically validated immunohistochemical assays for nuclear accumulation of p53 protein and PTEN protein loss, with sequencing confirmation of TP53 mutations in a subset...
January 4, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29295717/cribriform-and-intraductal-prostate-cancer-are-associated-with-increased-genomic-instability-and-distinct-genomic-alterations
#4
René Böttcher, Charlotte F Kweldam, Julie Livingstone, Emilie Lalonde, Takafumi N Yamaguchi, Vincent Huang, Fouad Yousif, Michael Fraser, Robert G Bristow, Theodorus van der Kwast, Paul C Boutros, Guido Jenster, Geert J L H van Leenders
BACKGROUND: Invasive cribriform and intraductal carcinoma (CR/IDC) is associated with adverse outcome of prostate cancer patients. The aim of this study was to determine the molecular aberrations associated with CR/IDC in primary prostate cancer, focusing on genomic instability and somatic copy number alterations (CNA). METHODS: Whole-slide images of The Cancer Genome Atlas Project (TCGA, N = 260) and the Canadian Prostate Cancer Genome Network (CPC-GENE, N = 199) radical prostatectomy datasets were reviewed for Gleason score (GS) and presence of CR/IDC...
January 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29284790/prostate-specific-pten-deletion-in-mice-activates-inflammatory-microrna-expression-pathways-in-the-epithelium-early-in-hyperplasia-development
#5
D Alwyn Dart, Pinar Uysal-Onganer, W G Jiang
PTen loss is one of the most frequent events in prostate cancer both at the initiation stage and during late stage metastatic development. The mouse model of prostate-specific probasin-mediated Pten deletion leads to prostate intraepithelial neoplasia (PIN) leading to adenocarcinoma. Using this model, we analysed the miR and mRNA transcriptome profile of Pten -/- PIN versus wild type age-matched prostate tissues and analysed the effects of Pten loss on miR expression in the early neoplastic process. At the PIN stage, Pten loss significantly changed the expression of over 20 miRNAs and over 4000 genes...
December 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29261439/targeting-androgen-receptor-and-dna-repair-in-metastatic-castration-resistant-prostate-cancer-results-from-nci-9012
#6
Maha Hussain, Stephanie Daignault-Newton, Przemyslaw W Twardowski, Costantine Albany, Mark N Stein, Lakshmi P Kunju, Javed Siddiqui, Yi-Mi Wu, Dan Robinson, Robert J Lonigro, Xuhong Cao, Scott A Tomlins, Rohit Mehra, Kathleen A Cooney, Bruce Montgomery, Emmanuel S Antonarakis, Daniel H Shevrin, Paul G Corn, Young E Whang, David C Smith, Megan V Caram, Karen E Knudsen, Walter M Stadler, Felix Y Feng, Arul M Chinnaiyan
Purpose To determine whether cotargeting poly (ADP-ribose) polymerase-1 plus androgen receptor is superior to androgen receptor inhibition in metastatic castration-resistant prostate cancer (mCRPC) and whether ETS fusions predict response. Patients and Methods Patients underwent metastatic site biopsy and were stratified by ETS status and randomly assigned to abiraterone plus prednisone without (arm A) or with veliparib (arm B). Primary objectives were: confirmed prostate-specific antigen (PSA) response rate (RR) and whether ETS fusions predicted response...
December 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29229583/integrative-genomic-analysis-of-coincident-cancer-foci-implicates-ctnnb1-and-pten-alterations-in-ductal-prostate-cancer
#7
Marc Gillard, Justin Lack, Andrea Pontier, Divya Gandla, David Hatcher, Adam G Sowalsky, Jose Rodriguez-Nieves, Donald Vander Griend, Gladell Paner, David VanderWeele
BACKGROUND: Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. OBJECTIVE: To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient...
December 8, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29228234/tgfbr2-inactivation-facilitates-cellular-plasticity-and-development-of-pten-null-prostate-cancer
#8
Wei Zhao, Peng Tan, Qingyuan Zhu, Adebusola Ajibade, Teng Long, Wenyong Long, Qingtian Li, Pinghua Liu, Bo Ning, Helen Y Wang, Rong-Fu Wang
Mutations in tumors can create a state of increased cellular plasticity that promotes resistance to treatment. Thus, there is an urgent need to develop novel strategies for identifying key factors that regulate cellular plasticity in order to combat resistance to chemotherapy and radiation treatment. Here we report that prostate epithelial cell reprogramming could be exploited to identify key factors required for promoting prostate cancer tumorigenesis and cellular plasticity. Deletion of phosphatase and tensin homolog (Pten) and transforming growth factor-beta receptor type 2 (Tgfbr2) may increase prostate epithelial cell reprogramming efficiency in vitro and cause rapid tumor development and early mortality in vivo...
December 8, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29225123/clinical-utility-and-biologic-implications-of-phosphatase-and-tensin-homolog-pten-and-ets-related-gene-erg-in-prostate-cancer
#9
REVIEW
David Ullman, David Dorn, Soroush Rais-Bahrami, Jennifer Gordetsky
Phosphatase and Tensin Homolog (PTEN) and ETS-related Gene (ERG) mutations are commonly found in prostate cancer. Although mouse studies have demonstrated PTEN and ERG cooperatively interact during tumorigenesis, human studies examining these genes have been inconclusive. A systematic Pubmed search including original articles assessing the pathogenesis of PTEN and ERG in prostate cancer was performed. Studies examining ERG's prognostic significance have conflicting results. Studies examining PTEN and ERG simultaneously found these genes are likely to occur together but cooperative tumorigenesis functions have not been conclusively established...
December 7, 2017: Urology
https://www.readbyqxmd.com/read/29206995/concordance-of-circulating-tumor-dna-and-matched-metastatic-tissue-biopsy-in-prostate-cancer
#10
Alexander W Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M Beer, Joshi J Alumkal, George V Thomas, Robert E Reiter, Matthew B Rettig, Christopher P Evans, Allen C Gao, Kim N Chi, Eric J Small, Martin E Gleave
Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling...
December 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29199015/contemporary-prognostic-indicators-for-prostate-cancer-incorporating-international-society-of-urological-pathology-recommendations
#11
REVIEW
Lars Egevad, Brett Delahunt, Glen Kristiansen, Hemamali Samaratunga, Murali Varma
Prognostic assessment is a key element in the management of patients with prostate cancer as it informs both treatment, follow-up and outcome prediction. Tumour grade should be based upon the novel and evidence-based recommendations of the International Society of Urological Pathology (ISUP) Consensus Conference of 2014, with ISUP grades 1-5 being derived from 2005 ISUP modified Gleason grading, i.e., ISUP grade 1 (3 + 3 = 6), grade 2 (3 + 4 = 7), grade 3 (4 + 3 = 7), grade 4 (3 + 5 = 8, 5 + 3 = 8, 4 + 4 = 8), and grade 5 (4 + 5 = 9 5 + 4 = 9, 5 + 5 = 10)...
November 30, 2017: Pathology
https://www.readbyqxmd.com/read/29185453/dysregulation-of-yap-by-arf-stimulated-with-tea-derived-carbon-nanodots
#12
Yingqiu Xie, Qinglei Sun, Ayan A Nurkesh, Jiang Lu, Sholpan Kauanova, Jinhong Feng, Darkhan Tursynkhan, Qing Yang, Aishabibi Kassymbek, Mirat Karibayev, Korlan Duisenova, Haiyan Fan, Xiao Wang, Limara Manarbek, Aisulu Maipas, Zhenbang Chen, Mannix P Balanay
YAP is a downstream nuclear transcription factor of Hippo pathway which plays an essential role in development, cell growth, organ size and homeostasis. It was previously identified that elevation of YAP in genomics of genetic engineered mouse (GEM) model of prostate cancer is associated with Pten/Trp53 inactivation and ARF elevation hypothesizing the essential crosstalk of AKT/mTOR/YAP with ARF in prostate cancer. However, the detailed function and trafficking of YAP in cancer cells remains unclear. Using GEM microarray model, we found ARF dysregulates Hippo and Wnt pathways...
November 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167276/pten-loss-promotes-intratumoral-androgen-synthesis-and-tumor-microenvironment-remodeling-via-aberrant-activation-of-runx2-in-castration-resistant-prostate-cancer
#13
Yinhui Yang, Yang Bai, Yundong He, Yu Zhao, Jiaxiang Chen, Linlin Ma, Yunqian Pan, Michael Hinten, Jun Zhang, R Jeffrey Karnes, Manish Kohli, Jennifer J Westendorf, Benyi Li, Runzhi Zhu, Haojie Huang, Wanhai Xu
PURPOSE: Intratumoral androgen synthesis (IAS) is a key mechanism promoting androgen receptor (AR) reactivation and anti-androgen resistance in castration-resistant prostate cancer (CRPC). However, signaling pathways driving aberrant IAS remain poorly understood.  Experimental Design: The effect of components of the AKT-RUNX2-osteocalcin (OCN)-GPRC6A-CREB signaling axis on expression of steroidogenesis genes CYP11A1 and CYP17A1 and testosterone level were examined in PTEN-null human PCa cell lines...
November 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29163708/mir-20b-promotes-cellular-proliferation-and-migration-by-directly-regulating-phosphatase-and-tensin-homolog-in-prostate-cancer
#14
Ju Guo, Zewen Xiao, Xingwei Yu, Runfu Cao
MicroRNAs are small non-coding RNAs, which are critical regulators of carcinogenesis and tumor progression. Previous studies have identified that microRNA-20b (miR-20b) acts as an oncogene in numerous cancers. However, the role of miR-20b in prostate cancer remains unclear. The present study aimed to investigate the expression of miR-20b in prostate cancer and to examine whether modulating miR-20b expression impacts prostate cancer cellular proliferation and migration. It was revealed that miR-20b was strongly expressed in prostate cancer tissues compared with adjacent normal prostate tissues (P<0...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142193/pten-is-a-protein-phosphatase-that-targets-active-ptk6-and-inhibits-ptk6-oncogenic-signaling-in-prostate-cancer
#15
Darren J Wozniak, Andre Kajdacsy-Balla, Virgilia Macias, Susan Ball-Kell, Morgan L Zenner, Wenjun Bie, Angela L Tyner
PTEN activity is often lost in prostate cancer. We show that the tyrosine kinase PTK6 (BRK) is a PTEN substrate. Phosphorylation of PTK6 tyrosine 342 (PY342) promotes activation, while phosphorylation of tyrosine 447 (PY447) regulates auto-inhibition. Introduction of PTEN into a PTEN null prostate cancer cell line leads to dephosphorylation of PY342 but not PY447 and PTK6 inhibition. Conversely, PTEN knockdown promotes PTK6 activation in PTEN positive cells. Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#16
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29137428/pten-loss-is-associated-with-prostate-cancer-recurrence-and-alterations-in-tumor-dna-methylation-profiles
#17
Milan S Geybels, Min Fang, Jonathan L Wright, Xiaoyu Qu, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Ziding Feng, Elaine A Ostrander, Peter S Nelson, Janet L Stanford
Background: Prostate cancer (PCa) with loss of the tumor suppressor gene PTEN has an unfavorable prognosis. DNA methylation profiles associated with PTEN loss may provide further insights into the mechanisms underlying these more aggressive, clinically relevant tumors. Methods: The cohort included patients with clinically localized PCa. Samples taken from the primary tumor were used to determine PTEN genomic deletions using FISH, and to analyze epigenome-wide DNA methylation profiles...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134654/pten-loss-and-activation-of-k-ras-and-%C3%AE-catenin-cooperate-to-accelerate-prostate-tumourigenesis
#18
Matthew T Jefferies, Adam C Cox, Boris Y Shorning, Valerie Meniel, David Griffiths, Howard G Kynaston, Matthew J Smalley, Alan R Clarke
Aberrant phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) and WNT signalling are emerging as key events in the multistep nature of prostate tumourigenesis and progression. Here, we report a compound prostate cancer murine model in which these signalling pathways cooperate to produce a more aggressive prostate cancer phenotype. Using Cre-LoxP technology and the probasin promoter, we combined the loss of Pten (Pten(fl/fl) ), to activate the PI3K signalling pathway, with either dominant stabilized β-catenin [Catnb(+/lox(ex3)) ] or activated K-RAS (K-Ras(+/V12) ) to aberrantly activate WNT and MAPK signalling, respectively...
December 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29123407/association-of-pten-expression-with-biochemical-recurrence-in-prostate-cancer-results-based-on-previous-reports
#19
Haijie Xie, Bin Xie, Chunyu Liu, Jun Wang, Yong Xu
Purpose: Among men, prostate cancer (PCa) is one of the most commonly diagnosed cancers and the leading cause of cancer death worldwide. Phosphatase and tension homolog (PTEN) acts as a negative regulator of the phosphatidylinositol 3-kinase (PIK3)/Akt pathway and suppresses tumor progression. Meanwhile, PTEN is frequently deleted in PCa. Identifying the specific molecular markers of biochemical recurrence (BCR) in PCa patients is critical in clinical practice. Our systematic review summarizes the evidence about the PTEN expression and BCR rate in PCa patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29121168/%C3%AE-tocopherol-inhibits-the-development-of-prostate-adenocarcinoma-in-prostate-specific-pten-mice
#20
Hong Wang, Xu Yang, Anna Liu, Guocan Wang, Maarten C Bosland, Chung S Yang
The PTEN/PI3K/AKT axis plays a critical role in regulating cell growth, differentiation and survival. Activation of this signaling pathway is frequently found in human cancers. Our previous studies demonstrated that δ-tocopherol (δ-T) attenuates the activation of AKT by growth factor in prostate cancer cell lines, leading to inhibition of proliferation and induction of apoptosis. Herein, we investigated whether δ-T inhibits the development of prostate adenocarcinoma in prostate-specific Pten-/- (Ptenp-/-) mice in which the activation of AKT is the major driving force for tumorigenesis...
November 7, 2017: Carcinogenesis
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