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Xu Li, Wenqi Wang, Yuanxin Xi, Min Gao, MyKim Tran, Kathryn E Aziz, Jun Qin, Wei Li, Junjie Chen
By combining the results of a large-scale proteomic analysis of the human transcription factor interaction network with knowledge databases, we identified FOXR2 as one of the top-ranked candidate proto-oncogenes. Here, we show that FOXR2 forms a stable complex with MYC and MAX and subsequently regulates cell proliferation by promoting MYC's transcriptional activities. We demonstrate that FOXR2 is highly expressed in several breast, lung, and liver cancer cell lines and related patient tumor samples, while reduction of FOXR2 expression in a xenograft model inhibits tumor growth...
July 12, 2016: Cell Reports
Dominik Sturm, Brent A Orr, Umut H Toprak, Volker Hovestadt, David T W Jones, David Capper, Martin Sill, Ivo Buchhalter, Paul A Northcott, Irina Leis, Marina Ryzhova, Christian Koelsche, Elke Pfaff, Sariah J Allen, Gnanaprakash Balasubramanian, Barbara C Worst, Kristian W Pajtler, Sebastian Brabetz, Pascal D Johann, Felix Sahm, Jüri Reimand, Alan Mackay, Diana M Carvalho, Marc Remke, Joanna J Phillips, Arie Perry, Cynthia Cowdrey, Rachid Drissi, Maryam Fouladi, Felice Giangaspero, Maria Łastowska, Wiesława Grajkowska, Wolfram Scheurlen, Torsten Pietsch, Christian Hagel, Johannes Gojo, Daniela Lötsch, Walter Berger, Irene Slavc, Christine Haberler, Anne Jouvet, Stefan Holm, Silvia Hofer, Marco Prinz, Catherine Keohane, Iris Fried, Christian Mawrin, David Scheie, Bret C Mobley, Matthew J Schniederjan, Mariarita Santi, Anna M Buccoliero, Sonika Dahiya, Christof M Kramm, André O von Bueren, Katja von Hoff, Stefan Rutkowski, Christel Herold-Mende, Michael C Frühwald, Till Milde, Martin Hasselblatt, Pieter Wesseling, Jochen Rößler, Ulrich Schüller, Martin Ebinger, Jens Schittenhelm, Stephan Frank, Rainer Grobholz, Istvan Vajtai, Volkmar Hans, Reinhard Schneppenheim, Karel Zitterbart, V Peter Collins, Eleonora Aronica, Pascale Varlet, Stephanie Puget, Christelle Dufour, Jacques Grill, Dominique Figarella-Branger, Marietta Wolter, Martin U Schuhmann, Tarek Shalaby, Michael Grotzer, Timothy van Meter, Camelia-Maria Monoranu, Jörg Felsberg, Guido Reifenberger, Matija Snuderl, Lynn Ann Forrester, Jan Koster, Rogier Versteeg, Richard Volckmann, Peter van Sluis, Stephan Wolf, Tom Mikkelsen, Amar Gajjar, Kenneth Aldape, Andrew S Moore, Michael D Taylor, Chris Jones, Nada Jabado, Matthias A Karajannis, Roland Eils, Matthias Schlesner, Peter Lichter, Andreas von Deimling, Stefan M Pfister, David W Ellison, Andrey Korshunov, Marcel Kool
Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features...
February 25, 2016: Cell
Xiao Wang, Bin He, Yong Gao, Yandong Li
Forkhead box R2 (FOXR2), a member of forkhead box (FOX) family, has been identified as an oncogene in medulloblastoma and breast cancer recently. However, the expression and function of FOXR2 in hepatocellular carcinoma cell (HCC) are still unclear. Here, we report that FOXR2 is frequently upregulated in 25/42 (59.5 %) of HCC specimens compared with neighboring non-cancerous tissues in messenger RNA (mRNA) level and further confirmed by immunohistochemistry analysis in protein level. Cellular function analyses revealed that FOXR2 promoted cell growth and colony formation, whereas knockdown of FOXR2 by RNA inference inhibited cell growth and decreased the growth ability of HCC cells in soft agar...
August 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Haiping Song, Wenshan He, Xiaoqing Huang, Huiqiong Zhang, Tao Huang
Forkhead box protein R2 (FOXR2) is associated with human central nervous system neoplasms. However, the expression level of FOXR2 in breast cancer specimens remains largely unknown. To identify whether FOXR2 can serve as a biomarker for the diagnosis and prognosis of breast cancer, real-time PCR and immunohistochemistry (IHC) staining were utilized to detect the expression of FOXR2. The messenger RNA (mRNA) and protein levels of FOXR2 in breast cancer samples were novelty higher compared to non-tumorous breast tissues...
May 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Stefan Nagel, Corinna Meyer, Maren Kaufmann, Hans G Drexler, Roderick A F MacLeod
FOX genes encode transcription factors which regulate basic developmental processes during embryogenesis and in the adult. Several FOX genes show deregulated expression in particular malignancies, representing oncogenes or tumor suppressors. Here, we screened six Hodgkin lymphoma (HL) cell lines for FOX gene activity by comparative microarray profiling, revealing overexpression of FOXC1 and FOXD1, and reduced transcription of FOXN3, FOXO1, and FOXP1. In silico expression analyses of these FOX gene candidates in HL patient samples supported the cell line data...
November 2014: Genes, Chromosomes & Cancer
Hideto Koso, Asano Tsuhako, Eli Lyons, Jerrold M Ward, Alistair G Rust, David J Adams, Nancy A Jenkins, Neal G Copeland, Sumiko Watanabe
Medulloblastoma is the most common pediatric brain tumor, and in ∼25% of cases, it is driven by aberrant activation of the Sonic Hedgehog (SHH) pathway in granule neuron precursor (GNP) cells. In this study, we identified novel medulloblastoma driver genes through a transposon mutagenesis screen in the developing brain of wild-type and Trp53 mutant mice. Twenty-six candidates were identified along with established driver genes such as Gli1 and Crebbp. The transcription factor FoxR2, the most frequent gene identified in the screen, is overexpressed in a small subset of human medulloblastoma of the SHH subtype...
April 15, 2014: Cancer Research
Eric P Rahrmann, Adrienne L Watson, Vincent W Keng, Kwangmin Choi, Branden S Moriarity, Dominic A Beckmann, Natalie K Wolf, Aaron Sarver, Margaret H Collins, Christopher L Moertel, Margaret R Wallace, Bernat Gel, Eduard Serra, Nancy Ratner, David A Largaespada
Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas of Schwann cell lineage origin that occur sporadically or in association with the inherited syndrome neurofibromatosis type 1. To identify genetic drivers of MPNST development, we used the Sleeping Beauty (SB) transposon-based somatic mutagenesis system in mice with somatic loss of transformation-related protein p53 (Trp53) function and/or overexpression of human epidermal growth factor receptor (EGFR). Common insertion site (CIS) analysis of 269 neurofibromas and 106 MPNSTs identified 695 and 87 sites with a statistically significant number of recurrent transposon insertions, respectively...
July 2013: Nature Genetics
Masuko Katoh, Masaru Katoh
Forkhead-box (FOX) superfamily genes are implicated in carcinogenesis through gene amplification, retroviral integration and chromosomal translocation. FOX superfamily genes within the human genome are classified into 17 or 18 families, designated FOX# (# is alphabet A-Q or R). FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1) and FOXN6 (FOXR2) genes constitute the FOXN gene family. Here, we characterized human FOXN4 gene by using bioinformatics. FOXN4 gene at human chromosome 12q24.12 was found to encode three isoforms...
November 2004: International Journal of Molecular Medicine
Masuko Katoh, Masaru Katoh
Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. FOXE3-FOXD2 (1p33), FOXQ1-FOXF2-FOXC1 (6p25...
November 2004: International Journal of Oncology
Masuko Katoh, Masaru Katoh
Amplified region (amplicon) around MLL gene is closely linked to the 11q23.3 commonly deleted region of neuroblastoma, which includes cancer-associated genes such as PHLDB1 (LL5A), BCL9L, FOXN5 (FOXR1), CBL, MFRP, and PVRL1 (Nectin) genes. FOXN6 (FOXR2) gene at human chromosome Xp11.21 is generated due to retrotransposition of ancestral Foxn5 gene during evolution. FOXN5 and FOXN6 orthologs share the common domain structure consisting of FN56 and Forhead-box (FOX) domains. Here, we identified and characterized mouse Foxn5 gene by using bioinformatics...
September 2004: International Journal of Molecular Medicine
Masuko Katoh, Masaru Katoh
Forkhead-box (FOX) family transcription factors are implicated in carcinogenesis and embryogenesis. Here, we identified and characterized the human FOXK1 gene by using bioinformatics. Complete coding sequence of human FOXK1 cDNA was determined by assembling CB959941 EST, AW206906 EST, and 5'-truncated FLJ16099 (AK122663.1) cDNA. FOXK1 gene, consisting of nine exons, was mapped to human chromosome 7p22.1. Mouse Foxk1 (NM_199068.1) was an aberrant cDNA with frame shifts due to multiple insertions and deletions, while mouse IMAGE6853263 (BC060238...
July 2004: International Journal of Molecular Medicine
Masuko Katoh, Masaru Katoh
Forkhead-box (FOX) transcription factors are implicated in carcinogenesis through gene amplification, retroviral integration, or chromosomal translocation. FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4 and FOXN5 (FOXR1) constitute the FOXN family. Here, we identified and characterized human FOXN6 (FOXR2) and rodent Foxn6 (Foxr2) orthologs by using bioinformatics. Human FOXN6 gene was identified within human genome sequence RP11-167P23 (AL159987.19), mouse Foxn6 gene within mouse genome sequence RP23-180D16 (AL672293...
July 2004: International Journal of Oncology
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