Nuclear Hormone Receptor NR4A2 Is Involved in Cell Transformation and Apoptosis
Open Access
- 15 November 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 64 (22), 8208-8212
- https://doi.org/10.1158/0008-5472.can-04-2134
Abstract
HeLaHF cells are transformation revertants of cervical cancer HeLa cells and have lost anchorage-independent growth potential and tumorigenicity. Activation of tumor suppressor(s) was implicated previously in this transformation reversion. In this study, expression profiling analysis was carried out to identify potential oncogenes that are down-regulated in HeLaHF cells. We found that all three members of the NR4A1/Nur77/NGFIB orphan nuclear hormone receptor subfamily (NR4A1, NR4A2, and NR4A3) were down-regulated in the HeLaHF revertant. Small interfering RNA-mediated down-regulation of NR4A2 in HeLa cells, either transiently or stably, resulted in reduced anchorage-independent growth that was largely attributable to increased anoikis. Furthermore, down-regulation of NR4A2 as well as NR4A1 promoted intrinsic apoptosis. These phenotypes were also observed in several other experimental cancer cells, suggesting the observed apoptosis suppression is a more general property of NR4A2 and NR4A1. These phenotypes also suggest that the Nur77/NGFIB subfamily of orphan receptors exhibit certain oncogenic functionalities with regards to cell proliferation and apoptosis and could therefore be evaluated as potential cancer therapeutic targets.Keywords
This publication has 32 references indexed in Scilit:
- A functional genomics approach for the identification of putative tumor suppressor genes: Dickkopf-1 as suppressor of HeLa cell transformationCarcinogenesis: Integrative Cancer Research, 2004
- The Orphan Steroid Receptor Nur77 Family Member Nor-1 Is Essential for Early Mouse EmbryogenesisPublished by Elsevier BV ,2003
- Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptorsNature, 2003
- Nuclear Receptors Nor1 and NGFI-B/Nur77 Play Similar, Albeit Distinct, Roles in the Hypothalamo-Pituitary-Adrenal AxisEndocrinology, 2000
- Identification and Validation of a Gene Involved in Anchorage-Independent Cell Growth Control Using a Library of Randomized Hairpin RibozymesGenomics, 2000
- Ceramide-induced cell death is independent of the Fas/Fas ligand pathway and is prevented by Nur77 overexpression in A20 B cellsCell Death & Differentiation, 2000
- Reduced Nurrl Expression Increases the Vulnerability of Mesencephalic Dopamine Neurons to MPTP‐Induced InjuryJournal of Neurochemistry, 1999
- Dopamine Biosynthesis Is Selectively Abolished in Substantia Nigra/Ventral Tegmental Area but Not in Hypothalamic Neurons in Mice with Targeted Disruption of the Nurr1 GeneMolecular and Cellular Neuroscience, 1998
- Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1Molecular Endocrinology, 1996
- A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selectionImmunity, 1995