ID1 and ID2 are retinoic acid responsive genes and induce a G0/G1 accumulation in acute promyelocytic leukemia cells

Autor: B.A. van der Reijden, Joop H. Jansen, Claudia A.J. Erpelinck-Verschueren, M.C. Breems-de Ridder, Bob Löwenberg, Gorica Nikoloski, S. van Wageningen, T. de Witte, Jeannet Nigten, P. B. Van Hennik
Přispěvatelé: Hematology, Virology
Rok vydání: 2005
Předmět:
Inhibitor of Differentiation Protein 1
Acute promyelocytic leukemia
Cancer Research
medicine.drug_class
Retinoic acid
Tretinoin
Biology
Resting Phase
Cell Cycle
Translocation
Genetic
Colony-Forming Units Assay
chemistry.chemical_compound
Leukemia
Promyelocytic
Acute
Downregulation and upregulation
Immune Regulation [NCMLS 2]
Translational research [ONCOL 3]
immune system diseases
Cell Line
Tumor
Basic Helix-Loop-Helix Transcription Factors
medicine
Humans
Iron metabolism [IGMD 7]
Retinoid
neoplasms
Transcription factor
Cells
Cultured
Cell Proliferation
Inhibitor of Differentiation Protein 2
Molecular diagnosis
prognosis and monitoring [UMCN 1.2]
Dose-Response Relationship
Drug
Basic helix-loop-helix
G1 Phase
Cell Differentiation
Hematology
medicine.disease
Clone Cells
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Repressor Proteins
Pathogenesis and modulation of inflammation [N4i 1]
Oncology
chemistry
Cell culture
Cancer research
Signal transduction
Transcription Factors
Zdroj: Leukemia, 19(5), 799-805. Nature Publishing Group
Leukemia, 19, 799-805
Leukemia, 19, 5, pp. 799-805
ISSN: 1476-5551
0887-6924
Popis: Contains fulltext : 47334.pdf (Publisher’s version ) (Closed access) Acute promyelocytic leukemia (APL) is uniquely sensitive to treatment with all-trans retinoic acid (ATRA), which results in the expression of genes that induce the terminal granulocytic differentiation of the leukemic blasts. Here we report the identification of two ATRA responsive genes in APL cells, ID1 and ID2. These proteins act as antagonists of basic helix-loop-helix (bHLH) transcription factors. ATRA induced a rapid increase in ID1 and ID2, both in the APL cell line NB4 as well as in primary patient cells. In addition, a strong downregulation of E2A was observed. E2A acts as a general heterodimerization partner for many bHLH proteins that are involved in differentiation control in various tissues. The simultaneous upregulation of ID1 and ID2, and the downregulation of E2A suggest a role for bHLH proteins in the induction of differentiation of APL cells following ATRA treatment. To test the relevance of this upregulation, ID1 and ID2 were overexpressed in NB4 cells. Overexpression inhibited proliferation and induced a G0/G1 accumulation. These results indicate that ID1 and ID2 are important retinoic acid responsive genes in APL, and suggest that the inhibition of specific bHLH transcription factor complexes may play a role in the therapeutic effect of ATRA in APL.
Databáze: OpenAIRE
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