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Citations to this article

The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers
Enrique Zudaire, … , Michael Birrer, Frank Cuttitta
Enrique Zudaire, … , Michael Birrer, Frank Cuttitta
Published January 2, 2008
Citation Information: J Clin Invest. 2008;118(2):640-650. https://doi.org/10.1172/JCI30024.
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The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers

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Abstract

The aryl hydrocarbon receptor repressor (AHRR) is a bHLH/Per-ARNT-Sim transcription factor located in a region of chromosome 5 (5p15.3) that has been proposed to contain one or more tumor suppressor genes. We report here consistent downregulation of AHRR mRNA in human malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, and ovary, and demonstrate DNA hypermethylation as the regulatory mechanism of AHRR gene silencing. Knockdown of AHRR gene expression in a human lung cancer cell line using siRNA significantly enhanced in vitro anchorage-dependent and -independent cell growth as well as cell growth after transplantation into immunocompromised mice. In addition, knockdown of AHRR in non-clonable normal human mammary epithelial cells enabled them to grow in an anchorage-independent manner. Further, downregulation of AHRR expression in the human lung cancer cell line conferred resistance to apoptotic signals and enhanced motility and invasion in vitro and angiogenic potential in vivo. Ectopic expression of AHRR in tumor cells resulted in diminished anchorage-dependent and -independent cell growth and reduced angiogenic potential. These results therefore demonstrate that AHRR is a putative new tumor suppressor gene in multiple types of human cancers.

Authors

Enrique Zudaire, Natalia Cuesta, Vundavalli Murty, Karen Woodson, Lisa Adams, Nieves Gonzalez, Alfredo Martínez, Gopeshwar Narayan, Ilan Kirsch, Wilbur Franklin, Fred Hirsch, Michael Birrer, Frank Cuttitta

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American journal of physiology. Gastrointestinal and liver physiology 2012
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S Portal-Nunez, UT Shankavaram, M Rao, N Datrice, S Atay, M Aparicio, KA Camphausen, PM Fernandez-Salguero, H Chang, P Lin, DS Schrump, S Garantziotis, F Cuttitta, E Zudaire
Cancer research 2012
A novel in vitro pancreatic carcinogenesis model
HJ Kang, YB Hong, HJ Kim, YW Yi, RG Nath, YS Chang, HC Cho, I Bae
Toxicology Letters 2011
Malignant Transformation of Mammary Epithelial Cells by Ectopic Overexpression of the Aryl Hydrocarbon Receptor
J B, SE E
Current cancer drug targets 2011
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor.
Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, Schumacher T, Jestaedt L, Schrenk D, Weller M, Jugold M, Guillemin GJ, Miller CL, Lutz C, Radlwimmer B, Lehmann I, von Deimling A, Wick W, Platten M
Nature 2011
Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast
JS Bae, JS Choi, SH Baik, WC Park, BJ Song, JS Kim, Y Lim, SS Jung
World journal of surgical oncology 2010
miR-125b promotes growth of prostate cancer xenograft tumor through targeting pro-apoptotic genes
XB Shi, L Xue, AH Ma, CG Tepper, HJ Kung, RW White
The Prostate 2010
Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli.
Fujii-Kuriyama Y, Kawajiri K
Proceedings of the Japan Academy. Series B, Physical and biological sciences 2010
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women
AL van Dyke, ML Cote, AS Wenzlaff, J Abrams, S Land, P Iyer, AG Schwartz
Journal of Cancer Epidemiology 2009
Characterization of MCF mammary epithelial cells overexpressing the Arylhydrocarbon receptor (AhR)
PS Wong, W Li, CF Vogel, F Matsumura
BMC Cancer 2009
The active form of human aryl hydrocarbon receptor (AHR) repressor lacks exon 8, and its Pro 185 and Ala 185 variants repress both AHR and hypoxia-inducible factor
SI Karchner, MJ Jenny, AM Tarrant, BR Evans, HJ Kang, I Bae, DH Sherr, ME Hahn
Molecular and cellular biology 2009
SUMO modification regulates the transcriptional repressor function of aryl hydrocarbon receptor repressor
M Oshima, J Mimura, H Sekine, H Okawa, Y Fujii-Kuriyama
The Journal of biological chemistry 2009
Epidermal growth factor-activated aryl hydrocarbon receptor nuclear translocator/HIF-1{beta} signal pathway up-regulates cyclooxygenase-2 gene expression associated with squamous cell carcinoma
KY Chang, MR Shen, MY Lee, WL Wang, WC Su, WC Chang, BK Chen
The Journal of biological chemistry 2009
Protocadherin PCDH10, Involved in Tumor Progression, is a Frequent and Early Target of Promoter Hypermethylation in Cervical Cancer
G Narayan, L Scotto, V Neelakantan, SH Kottoor, AH Wong, SL Loke, M Mansukhani, B Pothuri, JD Wright, AM Kaufmann, A Schneider, H Arias-Pulido, Q Tao, VV Murty
Genes, chromosomes & cancer 2009
The aryl hydrocarbon receptor (AhR) pathway as a regulatory pathway for cell adhesion and matrix metabolism
T Kung, KA Murphy, LA White
Biochemical Pharmacology 2008
Regulation of constitutive and inducible AHR signaling: complex interactions involving the AHR repressor
ME Hahn, LL Allan, DH Sherr
Biochemical Pharmacology 2008

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