HOX Genes in Pancreatic Development and Cancer
Abstract
The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are subsequently re-expressed in many types of cancer. Some recent studies have shown that HOX genes may have key roles both in pancreatic development and in adult diseases of the pancreas, including cancer. In this review we consider recent advances in elucidating the role of HOX genes in these processes, how they may connect early developmental events to subsequent adult disease, and their potential both as diagnostic markers and therapeutic targets.
Image: The arrangement of HOX genes in the mammalian genome.
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References
Abramovich C, Humphries RK. Hox regulation of normal and leukemic hematopoietic stem cells. Curr Opin Hematol 2005; 12:210-6. [PMID 15867577]
Iimura T, Pourquie O. Hox genes in time and space during vertebrate body formation. Dev Growth Differ 2007; 49:265-75. [PMID 17501904]
Moens CB, Selleri L. Hox cofactors in vertebrate development. Dev Biol 2006; 291:193-206. [PMID 16515781]
Scott MP. A rational nomenclature for vertebrate homeobox (HOX) genes. Nucleic Acids Res 1993; 21:1687-8. [PMID 8098522]
Hoegg S, Meyer A. Hox clusters as models for vertebrate genome evolution. Trends Genet 2005; 21:421-4. [PMID 15967537]
Knoepfler PS, Calvo KR, Chen H, Antonarakis SE, Kamps MP. Meis1 and pKnox1 bind DNA cooperatively with Pbx1 utilizing an interaction surface disrupted in oncoprotein E2a-Pbx1. Proc Natl Acad Sci U S A 1997; 94:14553-8. [PMID 9405651]
Phelan ML, Sadoul R, Featherstone MS. Functional differences between HOX proteins conferred by two residues in the homeodomain N-terminal arm. Mol Cell Biol 1994; 14:5066-75. [PMID 7913516]
Piper DE, Batchelor AH, Chang CP, Cleary ML, Wolberger C. Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation. Cell 1999; 96:587-97. [PMID 10052460]
Di-Poi N, Koch U, Radtke F, Duboule D. Additive and global functions of HoxA cluster genes in mesoderm derivatives. Dev Biol 2010; 341:488-98. [PMID 20303345]
Lappin TR, Grier DG, Thompson A, Halliday HL. HOX genes: seductive science, mysterious mechanisms. Ulster Med J 2006; 75:23-31. [PMID 16457401]
Morgan R. Hox genes: a continuation of embryonic patterning? Trends Genet 2006; 22:67-9. [PMID 16325300]
Lim H, Ma L, Ma WG, Maas RL, Dey SK. Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse. Mol Endocrinol 1999; 13:1005-17. [PMID 10379898]
Daniels TR, Neacato II, Rodríguez JA, Pandha HS, Morgan R, Penichet ML. Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells. Leukemia 2010; 24:1555-65. [PMID 20574452]
Morgan R, Pirard PM, Shears L, Sohal J, Pettengell R, Pandha HS. Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Res 2007; 67:5806-13. [PMID 17575148]
Morgan R, Plowright L, Harrington KJ, Michael A, Pandha HS. Targeting HOX and PBX transcription factors in ovarian cancer. BMC Cancer 2010;10:89. [PMID 20219106]
Plowright L, Harrington KJ, Pandha HS, Morgan R. HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer). Br J Cancer 2009; 100:470-5. [PMID 19156136]
Shears L, Plowright L, Harrington K, Pandha HS, Morgan R. Disrupting the interaction between HOX and PBX causes necrotic and apoptotic cell death in the renal cancer lines CaKi-2 and 769-P. J Urol 2008; 180:2196-201. [PMID 18804814]
Cordes R, Schuster-Gossler K, Serth K, Gossler A. Specification of vertebral identity is coupled to Notch signalling and the segmentation clock. Development 2004; 131:1221-33. [PMID 14960495]
Kawazoe Y, Sekimoto T, Araki M, Takagi K, Araki K, Yamamura K. Region-specific gastrointestinal Hox code during murine embryonal gut development. Dev Growth Differ 2002; 44:77-84. [PMID 11869294]
Tehrani Z, Lin S. Antagonistic interactions of hedgehog, Bmp and retinoic acid signals control zebrafish endocrine pancreas development. Development 2011; 138:631-40. [PMID 21228001]
Shi Y. Generation of functional insulin-producing cells from human embryonic stem cells in vitro. Methods Mol Biol 2010; 636:79-85. [PMID 20336517]
Langston AW, Gudas LJ. Retinoic acid and homeobox gene regulation. Curr Opin Genet Dev 1994; 4:550-5. [PMID 7950323]
Takács-Vellai K, Vellai T, Chen EB, Zhang Y, Guerry F, Stern MJ, Müller F. Transcriptional control of Notch signaling by a HOX and a PBX/EXD protein during vulval development in C. elegans. Dev Biol 2007; 302:661-9. [PMID 17084835]
Zakany J, Kmita M, Alarcon P, de la Pompa JL, Duboule D. Localized and transient transcription of Hox genes suggests a link between patterning and the segmentation clock. Cell 2001; 106:207-17. [PMID 11511348]
Lomberk GA, Imoto I, Gebelein B, Urrutia R, Cook TA. Conservation of the TGFbeta/Labial homeobox signaling loop in endoderm-derived cells between Drosophila and mammals. Pancreatology 2010; 10:74-84. [PMID 20339309]
Plaza S, Prince F, Adachi Y, Punzo C, Cribbs DL, Gehring WJ. Cross-regulatory protein-protein interactions between Hox and Pax transcription factors. Proc Natl Acad Sci U S A 2008; 105:13439-44. [PMID 18755899]
Nolte C, Rastegar M, Amores A, Bouchard M, Grote D, Maas R, et al. Stereospecificity and PAX6 function direct Hoxd4 neural enhancer activity along the antero-posterior axis. Dev Biol 2006; 299:582-93. [PMID 17010333]
Shah N, Sukumar S. The Hox genes and their roles in oncogenesis. Nat Rev Cancer 2010; 10:361-71. [PMID 20357775]
Aulisa L, Forraz N, McGuckin C, Hartgerink JD. Inhibition of cancer cell proliferation by designed peptide amphiphiles. Acta Biomater 2009; 5:842-53. [PMID 19249722]
Wallrapp C, Hahnel S, Muller-Pillasch F, Burghardt B, Iwamura T, Ruthenburger M, et al. A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res 2000; 60:2602-6. [PMID 10825129]
Arumugam T, Simeone DM, Van Golen K, Logsdon CD. S100P promotes pancreatic cancer growth, survival, and invasion. Clin Cancer Res 2005; 11:5356-64. [PMID 16061848]
Wu X, Chen H, Parker B, Rubin E, Zhu T, Lee JS, et al. HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition. Cancer Res 2006; 66:9527-34. [PMID 17018609]
De Souza Setubal Destro MF, Bitu CC, Zecchin KG, Graner E, Lopes MA, Kowalski LP, et al. Overexpression of HOXB7 homeobox gene in oral cancer induces cellular proliferation and is associated with poor prognosis. Int J Oncol 2010; 36:141-9. [PMID 19956843]
Chen H, Lee JS, Liang X, Zhang H, Zhu T, Zhang Z, et al. Hoxb7 inhibits transgenic HER-2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis. Cancer Res 2008; 68:3637-44. [PMID 18463397]
Nguyen A, Yang N, Dawson D. HOXB7 overexpression promotes pancreatic adenocarcinoma growth and invasion. AACR Meeting Abstracts 2009; 100th AACR Annual Meeting:4267.
Fischbach NA, Rozenfeld S, Shen W, Fong S, Chrobak D, Ginzinger D, et al. HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo. Blood 2005; 105:1456-66. [PMID 15522959]
Segara D, Biankin AV, Kench JG, Langusch CC, Dawson AC, Skalicky DA, et al. Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia. Clin Cancer Res 2005; 11:3587-96. [PMID 15867264]
Inamura K, Togashi Y, Ninomiya H, Shimoji T, Noda T, Ishikawa Y. HOXB2, an adverse prognostic indicator for stage I lung adenocarcinomas, promotes invasion by transcriptional regulation of metastasis-related genes in HOP-62 non-small cell lung cancer cells. Anticancer Res 2008; 28:2121-7. [PMID 18751384]
Asefa B, Dermott JM, Kaldis P, Stefanisko K, Garfinkel DJ, Keller JR. p205, a potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation. FEBS Lett 2006; 580:1205-14. [PMID 16458891]
Cantile M, Franco R, Tschan A, Baumhoer D, Zlobec I, Schiavo G, et al. HOX D13 expression across 79 tumor tissue types. Int J Cancer 2009; 125:1532-41. [PMID 19488988]
Weiss FU, Marques IJ, Woltering JM, Vlecken DH, Aghdassi A, Partecke LI, et al. Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer. Gastroenterology 2009; 137:2136-45. [PMID 19747919]
Prasad NB, Biankin AV, Fukushima N, Maitra A, Dhara S, Elkahloun AG, et al. Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. Cancer Res 2005; 65:1619-26. [PMID 15753353]
Raman V, Martensen SA, Reisman D, Evron E, Odenwald WF, Jaffee E, et al. Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature 2000; 405:974-8. [PMID 10879542]
Copyright (c) 2011 Sophie Gray, Hardev S Pandha, Agnieszka Michael, Gary Middleton, Richard Morgan
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