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PRKD1 in cancer

Caroline Spasojevic, Elisabetta Marangoni, Sophie Vacher, Franck Assayag, Didier Meseure, Sophie Château-Joubert, Martine Humbert, Manale Karam, Jean Marc Ricort, Christian Auclair, Marie Regairaz, Ivan Bièche
Protein Kinase D1 (PKD1) is a serine/threonine kinase encoded by the PRKD1 gene. PKD1 has been previously shown to be a prognostic factor in ERα+ tamoxifen-resistant breast tumors and PKD1 overexpression confers estrogen independence to ERα+ MCF7 cells. In the present study, our goal was to determine whether PKD1 is a prognostic factor and/or a relevant therapeutic target in breast cancer. We analyzed PRKD1 mRNA levels in 527 primary breast tumors. We found that high PRKD1 mRNA levels were significantly and independently associated with a low metastasis-free survival in the whole breast cancer population and in the triple-negative breast cancer (TNBC) subtype specifically...
May 1, 2018: Oncotarget
Bita Nickkholgh, Sivanandane Sittadjody, Michael B Rothberg, Xiaolan Fang, Kunzhao Li, Jeff W Chou, Gregory A Hawkins, K C Balaji
Down regulation of Protein Kinase D1 (PrKD1), a novel serine threonine kinase, in prostate, gastric, breast and colon cancers in humans leads to disease progression. While the down regulation of PrKD1 by DNA methylation in gastric cancer and by nuclear beta-catenin in colon cancer has been shown, the regulatory mechanisms in other cancers are unknown. Because we had demonstrated that PrKD1 is the only known kinase to phosphorylate threonine 120 (T120) of beta-catenin in prostate cancer resulting in increased nuclear beta-catenin, we explored the role of beta-catenin in gene regulation of PrKD1 ...
October 3, 2017: Oncotarget
Alena Skálová, Göran Stenman, Roderick H W Simpson, Henrik Hellquist, David Slouka, Tomas Svoboda, Justin A Bishop, Jennifer L Hunt, Ken-Ichi Nibu, Alessandra Rinaldo, Vincent Vander Poorten, Kenneth O Devaney, Petr Steiner, Alfio Ferlito
Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion...
February 2018: American Journal of Surgical Pathology
Heike Döppler, Richard Panayiotou, Elizabeth M Reid, Willibroad Maimo, Ligia Bastea, Peter Storz
Increased expression of PRKD1 and its gene product protein kinase D1 (PKD1) are linked to oncogenic signaling in pancreatic ductal adenocarcinoma, but a direct functional relationship to oncogenic KRas has not been established so far. We here describe the PRKD1 gene promoter as a target for oncogenic KRas signaling. We demonstrate that KRas-induced activation of the canonical NF-κB pathway is one mechanism of how PRKD1 expression is increased and identify the binding sites for NF-κB in the PRKD1 promoter...
September 21, 2016: Scientific Reports
Birgit Luef, Florian Handle, Gvantsa Kharaishvili, Martina Hager, Johannes Rainer, Günter Janetschek, Stephan Hruby, Christine Englberger, Jan Bouchal, Frédéric R Santer, Zoran Culig
Due to the urgent need for new prostate cancer (PCa) therapies, the role of androgen receptor (AR)-interacting proteins should be investigated. In this study we aimed to address whether the AR coactivator nuclear receptor coactivator 1 (NCOA1) is involved in PCa progression. Therefore, we tested the effect of long-term NCOA1 knockdown on processes relevant to metastasis formation. [(3)H]-thymidine incorporation assays revealed a reduced proliferation rate in AR-positive MDA PCa 2b and LNCaP cells upon knockdown of NCOA1, whereas AR-negative PC3 cells were not affected...
June 2016: Endocrine-related Cancer
H Majewska, A Skálová, I Weinreb, D Stodulski, M Hyrcza, C Stankiewicz, W Biernat
Cribriform adenocarcinoma of the tongue and minor salivary glands (CAMSG) was first described 16 years ago. It typically presents as a mass at the base of the tongue with early spread to lymph nodes, but without potential for distant metastases. In the 2005 World Health Organization Classification of Tumors the entity was classified as a possible variant of polymorphous low-grade adenocarcinoma (PLGA). Since then, more than 40 cases have been described in the English literature. Recently, PRKD1-3 translocation was found in more than 80% of CAMSGs...
March 2016: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Do Yeon Kim, Eun Young Park, EunSun Chang, Hyeok-Gu Kang, Yoonjin Koo, Eun Ji Lee, Je Yeong Ko, Hyun Kyung Kong, Kyung-Hee Chun, Jong Hoon Park
One of the properties of human breast cancer cells is cancer stemness, which is characterized by self-renewal capability and drug resistance. Protein kinase D1 (PRKD1) functions as a key regulator of many cellular processes and is downregulated in invasive breast cancer cells. In this study, we found that PRKD1 was upregulated in MCF-7-ADR human breast cancer cells characterized by drug resistance. Additionally, we discovered that PRKD1 expression was negatively regulated by miR-34a binding to the PRKD1 3'-UTR...
March 22, 2016: Oncotarget
Keeok Haam, Hee-Jin Kim, Kyung-Tae Lee, Jeong-Hwan Kim, Mirang Kim, Seon-Young Kim, Seung-Moo Noh, Kyu-Sang Song, Yong Sung Kim
BTB and CNC homology 2 (BACH2) is a lymphoid-specific transcription factor with a prominent role in B-cell development. Genetic polymorphisms within a single locus encoding BACH2 are associated with various autoimmune diseases and allergies. In this study, restriction landmark genomic scanning revealed methylation at a NotI site in a CpG island covering the BACH2 promoter in gastric cancer cell lines and primary gastric tumors. Increased methylation of the BACH2 promoter was observed in 52% (43/83) of primary gastric tumors, and BACH2 hypermethylation was significantly associated with decreased gene expression...
September 1, 2014: Cancer Letters
Hassan Brim, Mones S Abu-Asab, Mehdi Nouraie, Jose Salazar, Jim Deleo, Hadi Razjouyan, Pooneh Mokarram, Alejandro A Schaffer, Fakhraddin Naghibhossaini, Hassan Ashktorab
BACKGROUND: Different DNA aberrations processes can cause colorectal cancer (CRC). Herein, we conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients. MATERIALS AND METHODS: Array CGH was performed. The MSI phenotype and the methylation status of 15 genes was established using MSP. The CGH data was compared to two established lists of 41 and 68 cancer genes, respectively, and to CGH data from African Americans. A maximum parsimony cladogram based on global aberrations was established...
2014: PloS One
Sahra Borges, Heike Döppler, Edith A Perez, Cathy A Andorfer, Zhifu Sun, Panos Z Anastasiadis, E Thompson, Xochiquetzal J Geiger, Peter Storz
INTRODUCTION: DNA methylation-induced silencing of genes encoding tumor suppressors is common in many types of cancer, but little is known about how such epigenetic silencing can contribute to tumor metastasis. The PRKD1 gene encodes protein kinase D1 (PKD1), a serine/threonine kinase that is expressed in cells of the normal mammary gland, where it maintains the epithelial phenotype by preventing epithelial-to-mesenchymal transition. METHODS: The status of PRKD1 promoter methylation was analyzed by reduced representation bisulfite deep sequencing, methylation-specific PCR (MSP-PCR) and in situ MSP-PCR in invasive and noninvasive breast cancer lines, as well as in humans in 34 cases of "normal" tissue, 22 cases of ductal carcinoma in situ, 22 cases of estrogen receptor positive, HER2-negative (ER+/HER2-) invasive lobular carcinoma, 43 cases of ER+/HER2- invasive ductal carcinoma (IDC), 93 cases of HER2+ IDC and 96 cases of triple-negative IDC...
2013: Breast Cancer Research: BCR
Elena Fountzilas, Vassiliki Kotoula, Nikolaos Angouridakis, Ilias Karasmanis, Ralph M Wirtz, Anastasia G Eleftheraki, Elke Veltrup, Konstantinos Markou, Angelos Nikolaou, Dimitrios Pectasides, George Fountzilas
PURPOSE: Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. This study attempts to identify and independently validate gene expression models, prognostic of disease-free survival (DFS) in operable laryngeal cancer...
2013: PloS One
Fei Liang, Li Li, Maolin Wang, Xuyan Niu, Junping Zhan, Xiaojuan He, Changyuan Yu, Miao Jiang, Aiping Lu
ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicines (HMs) is one of the great herbal systems of the world, which play an important role in current health care system in many countries. In the view of tradition Chinese medicine (TCM) theory, Yin-yang and five-elements theory is the central theory, which is used to explain how the world and body work. Under the guidance of such philosophy, TCM considers that HMs have different properties, which are the important factors for prescribing herbal formulae; such prescriptions are based on TCM pattern classification in clinical practice...
July 30, 2013: Journal of Ethnopharmacology
X Xie, S-S Zhang, J Wen, H Yang, K-J Luo, F Yang, Y Hu, J-H Fu
Protein kinase D1 (PRKD1) is a kinase that regulates various pathways, which involve in cell proliferation, apoptosis, cell adhesion and invasion. Although PRKD1 expression has been observed in many cancers, its role in esophageal squamous cell cancer (ESCC) has not been well reported. As its dysregulation in cancers is organ specific, we sought to investigate the potential role of PRKD1 in the progression of ESCC. Samples were collected from 178 patients with completely resected ESCCs at Sun Yat-sen University Cancer Center, including 47 pairs of tumorous and non-tumorous tissues...
February 2014: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
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