This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Banham, A. H. Articles by Cordell, J. L. Search for Related Content PubMed PubMed Citation Articles by Banham, A. H. Articles by Cordell, J. L.

The FOXP1 Winged Helix Transcription Factor Is a Novel Candidate Tumor Suppressor Gene on Chromosome 3p¹

University of Oxford, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom [A. H. B., C. F., K. G., M. J., D. Y. M., J. L. C.]; Wharton Head and Neck Centre, Princess Margaret Hospital, Toronto, Ontario, M5G 2 M9 Canada [N. B.]; Laboratory of Pathology, Hospital Clinic, IDIBAPS, University of Barcelona, 08036-Barcelona, Spain [E. C., P. L. F.]; Life Science R&D, Amersham Pharmacia Biotech, Amersham Laboratories, Amersham, Bucks HP7 9NA, United Kingdom [J. E. P.]; Pathology Department, Haemek Medical Center, 18101, Afula, Israel [P. T.]; and Department of Pathology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, United Kingdom [K. W.]

The JC12 monoclonal antibody recognizes a previously unknown nuclear protein that showed a restricted distribution in normal tonsil and was also overexpressed in a subset of diffuse large B-cell lymphomas. Using this reagent, we expression cloned cDNAs encoding its antigenic target and identified this protein as a novel putative transcription factor, FOXP1. The FOXP1 protein sequence contains predicted domains characteristic of transcription factors, including a winged helix DNA-binding motif, a second potential DNA-binding motif, a C₂H₂ zinc finger, nuclear localization signals, coiled-coil regions, PEST sequences, and potential transactivation domains. The FOXP1 gene has been mapped to chromosome 3p14.1, a region that commonly shows loss of heterozygosity in a wide range of tumors and which is reported to contain a tumor suppressor gene(s). Using tissue arrays and immunohistochemistry, we demonstrate that both the FOXP1 mRNA and protein are widely expressed in normal tissues. The levels of FOXP1 mRNA were compared in paired normal and tumor tissues (from the same patient) using a tissue array containing cDNAs extracted from 68 samples taken from kidney, breast, prostate, uterus, ovary, cervix, colon, lung, stomach, rectum, small intestine, and from nine cancer cell lines. Differences in FOXP1 mRNA expression between normal and tumor samples were observed in 51% of cases. Most striking was the comparative loss of expression in 73% of colon tumors and comparative overexpression of FOXP1 mRNA in 75% of stomach tumors. Analysis of the FOXP1 mRNA expression in normal tissues (not taken from cancer patients) indicated that loss of FOXP1 expression may occur in some histologically normal tissues adjacent to tumors. Immunohistochemical analysis of FOXP1 protein expression was performed on 128 solid tumors, including 16 renal, 9 breast, 12 lung, 20 colon, 21 stomach, 10 head and neck, 35 prostate, and 5 pancreatic cases. Complete loss of expression, increased expression, and cytoplasmic mislocalization of the predominantly nuclear FOXP1 protein were frequently observed in neoplastic cells. Our study identifies FOXP1 as a new candidate tumor suppressor gene localized to the chromosome 3p14.1 region.

This article has been cited by other articles:

				M Rayoo, M Yan, E A Takano, G J Bates, P J Brown, A H Banham, and S B Fox Expression of the forkhead box transcription factor FOXP1 is associated with oestrogen receptor alpha, oestrogen receptor beta and improved survival in familial breast cancers J. Clin. Pathol., October 1, 2009; 62(10): 896 - 902. [Abstract] [Full Text] [PDF]

				W. W.L. Choi, D. D. Weisenburger, T. C. Greiner, M. A. Piris, A. H. Banham, J. Delabie, R. M. Braziel, H. Geng, J. Iqbal, G. Lenz, et al. A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy Clin. Cancer Res., September 1, 2009; 15(17): 5494 - 5502. [Abstract] [Full Text] [PDF]

				R. J. Ferland, L. F. Batiz, J. Neal, G. Lian, E. Bundock, J. Lu, Y.-C. Hsiao, R. Diamond, D. Mei, A. H. Banham, et al. Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia Hum. Mol. Genet., February 1, 2009; 18(3): 497 - 516. [Abstract] [Full Text] [PDF]

				U. Vinatzer, M. Gollinger, L. Mullauer, M. Raderer, A. Chott, and B. Streubel Mucosa-Associated Lymphoid Tissue Lymphoma: Novel Translocations Including Rearrangements of ODZ2, JMJD2C, and CNN3 Clin. Cancer Res., October 15, 2008; 14(20): 6426 - 6431. [Abstract] [Full Text] [PDF]

				B. Zhou, Q. Zhong, P. Minoo, C. Li, D. K. Ann, B. Frenkel, E. E. Morrisey, E. D. Crandall, and Z. Borok Foxp2 Inhibits Nkx2.1-Mediated Transcription of SP-C via Interactions with the Nkx2.1 Homeodomain Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 750 - 758. [Abstract] [Full Text] [PDF]

				T. Marafioti, J. C. Paterson, E. Ballabio, K. K. Reichard, S. Tedoldi, K. Hollowood, M. Dictor, M.-L. Hansmann, S. A. Pileri, M. J. Dyer, et al. Novel markers of normal and neoplastic human plasmacytoid dendritic cells Blood, April 1, 2008; 111(7): 3778 - 3792. [Abstract] [Full Text] [PDF]

				Lulu Fu, J. E. Girling, and P. A. W. Rogers Expression of Fox Head Protein 1 in Human Eutopic Endometrium and Endometriosis Reproductive Sciences, March 1, 2008; 15(3): 243 - 252. [Abstract] [PDF]

				P. J. Brown, S. L. Ashe, E. Leich, C. Burek, S. Barrans, J. A. Fenton, A. S. Jack, K. Pulford, A. Rosenwald, and A. H. Banham Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL Blood, March 1, 2008; 111(5): 2816 - 2824. [Abstract] [Full Text] [PDF]

				P. Arlotta, B. J. Molyneaux, D. Jabaudon, Y. Yoshida, and J. D. Macklis Ctip2 Controls the Differentiation of Medium Spiny Neurons and the Establishment of the Cellular Architecture of the Striatum J. Neurosci., January 16, 2008; 28(3): 622 - 632. [Abstract] [Full Text] [PDF]

				R. Sherva, P. Yue, G. Schonfeld, and R. J. Neuman Evidence for a quantitative trait locus affecting low levels of apolipoprotein B and low density lipoprotein on chromosome 10 in Caucasian families J. Lipid Res., December 1, 2007; 48(12): 2632 - 2639. [Abstract] [Full Text] [PDF]

				B. Li, A. Samanta, X. Song, K. T. Iacono, P. Brennan, T. A. Chatila, G. Roncador, A. H. Banham, J. L. Riley, Q. Wang, et al. FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX autoimmune disease Int. Immunol., July 1, 2007; 19(7): 825 - 835. [Abstract] [Full Text] [PDF]

				D. Angeloni Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease Brief Funct Genomic Proteomic, May 24, 2007; (2007) elm007v1. [Abstract] [Full Text] [PDF]

				W. Shu, M. M. Lu, Y. Zhang, P. W. Tucker, D. Zhou, and E. E. Morrisey Foxp2 and Foxp1 cooperatively regulate lung and esophagus development Development, May 15, 2007; 134(10): 1991 - 2000. [Abstract] [Full Text] [PDF]

				D. Pfeifer, M. Pantic, I. Skatulla, J. Rawluk, C. Kreutz, U. M. Martens, P. Fisch, J. Timmer, and H. Veelken Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays Blood, February 1, 2007; 109(3): 1202 - 1210. [Abstract] [Full Text] [PDF]

				X. Sagaert, P. de Paepe, L. Libbrecht, V. Vanhentenrijk, G. Verhoef, J. Thomas, I. Wlodarska, and C. De Wolf-Peeters Forkhead Box Protein P1 Expression in Mucosa-Associated Lymphoid Tissue Lymphomas Predicts Poor Prognosis and Transformation to Diffuse Large B-Cell Lymphoma J. Clin. Oncol., June 1, 2006; 24(16): 2490 - 2497. [Abstract] [Full Text] [PDF]

				P. Pajer, V. Pecenka, J. Kralova, V. Karafiat, D. Prukova, Z. Zemanova, R. Kodet, and M. Dvorak Identification of Potential Human Oncogenes by Mapping the Common Viral Integration Sites in Avian Nephroblastoma Cancer Res., January 1, 2006; 66(1): 78 - 86. [Abstract] [Full Text] [PDF]

				E. Bettelli, M. Dastrange, and M. Oukka Foxp3 interacts with nuclear factor of activated T cells and NF-{kappa}B to repress cytokine gene expression and effector functions of T helper cells PNAS, April 5, 2005; 102(14): 5138 - 5143. [Abstract] [Full Text] [PDF]

				A. H. Banham, J. M. Connors, P. J. Brown, J. L. Cordell, G. Ott, G. Sreenivasan, P. Farinha, D. E. Horsman, and R. D. Gascoyne Expression of the FOXP1 Transcription Factor Is Strongly Associated with Inferior Survival in Patients with Diffuse Large B-Cell Lymphoma Clin. Cancer Res., February 1, 2005; 11(3): 1065 - 1072. [Abstract] [Full Text] [PDF]

				B. Wang, J. Weidenfeld, M. M. Lu, S. Maika, W. A. Kuziel, E. E. Morrisey, and P. W. Tucker Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation Development, September 15, 2004; 131(18): 4477 - 4487. [Abstract] [Full Text] [PDF]

				M. Puig, M. Caceres, and A. Ruiz Silencing of a gene adjacent to the breakpoint of a widespread Drosophila inversion by a transposon-induced antisense RNA PNAS, June 15, 2004; 101(24): 9013 - 9018. [Abstract] [Full Text] [PDF]

				S. B. Fox, P. Brown, C. Han, S. Ashe, R. D. Leek, A. L. Harris, and A. H. Banham Expression of the Forkhead Transcription Factor FOXP1 Is Associated with Estrogen Receptor {alpha} and Improved Survival in Primary Human Breast Carcinomas Clin. Cancer Res., May 15, 2004; 10(10): 3521 - 3527. [Abstract] [Full Text] [PDF]

				S. Haesler, K. Wada, A. Nshdejan, E. E. Morrisey, T. Lints, E. D. Jarvis, and C. Scharff FoxP2 Expression in Avian Vocal Learners and Non-Learners J. Neurosci., March 31, 2004; 24(13): 3164 - 3175. [Abstract] [Full Text] [PDF]

				S. Li, J. Weidenfeld, and E. E. Morrisey Transcriptional and DNA Binding Activity of the Foxp1/2/4 Family Is Modulated by Heterotypic and Homotypic Protein Interactions Mol. Cell. Biol., January 15, 2004; 24(2): 809 - 822. [Abstract] [Full Text] [PDF]

				C. P. Hans, D. D. Weisenburger, T. C. Greiner, R. D. Gascoyne, J. Delabie, G. Ott, H. K. Muller-Hermelink, E. Campo, R. M. Braziel, E. S. Jaffe, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray Blood, January 1, 2004; 103(1): 275 - 282. [Abstract] [Full Text] [PDF]

				K. J. Savage, S. Monti, J. L. Kutok, G. Cattoretti, D. Neuberg, L. de Leval, P. Kurtin, P. D. Cin, C. Ladd, F. Feuerhake, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma Blood, December 1, 2003; 102(12): 3871 - 3879. [Abstract] [Full Text] [PDF]

				C. S. L. Lai, D. Gerrelli, A. P. Monaco, S. E. Fisher, and A. J. Copp FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder Brain, November 1, 2003; 126(11): 2455 - 2462. [Abstract] [Full Text] [PDF]

				W.A. Schulz, M. Burchardt, and M.V. Cronauer Molecular biology of prostate cancer Mol. Hum. Reprod., August 1, 2003; 9(8): 437 - 448. [Abstract] [Full Text] [PDF]

				B. Wang, D. Lin, C. Li, and P. Tucker Multiple Domains Define the Expression and Regulatory Properties of Foxp1 Forkhead Transcriptional Repressors J. Biol. Chem., June 27, 2003; 278(27): 24259 - 24268. [Abstract] [Full Text] [PDF]