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Retinoic acid up‐regulates nuclear retinoic acid receptor‐α expression in human neuroblastoma cells
Author(s) -
Wuarin Laura,
Chang Bieshia,
Wada Randal,
Sidell Neil
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560615
Subject(s) - retinoic acid , cycloheximide , northern blot , neuroblastoma , biology , retinoic acid receptor , receptor , retinoic acid inducible orphan g protein coupled receptor , retinoic acid receptor beta , retinoic acid receptor gamma , nuclear receptor , messenger rna , transcription factor , retinoid x receptor gamma , microbiology and biotechnology , western blot , cell culture , endocrinology , gene expression , tretinoin , protein biosynthesis , gene , biochemistry , genetics
Retinoic acid (RA) nuclear receptors (RARs) are thought to mediate the cellular and molecular effects of RA on a wide variety of tissues. In most cell types, RARα expression remains relatively constant following exposure to RA, while that of RARβ is rapidly induced. In this study, we show that in human neuroblastoma, a cell type exceptionally sensitive to RA‐induced differentiation, RARα as well as RARβ is markedly up‐regulated by RA treatment. This effect was consistent in all 5 neuroblastoma cell lines tested and was reflected in a 2‐to 5‐fold increase in receptor mRNA levels as assessed by Northern‐blot analysis. Using LA‐N‐5 human neuroblastoma cells, we found that receptor up‐regulation occurred in a time‐and dose‐dependent fashion with increases in both RARα and β mRNA detectable 1–2 hr after the addition of RA. These inductions were not abrogated by cycloheximide, indicating that protein synthesis was not required for the RA responses. Nuclear run‐off experiments combined with Northern‐blot analysis of RARα stability directly demonstrated that the up‐regulation of RARα mRNA levels reflected an increased rate of transcription without changes in message half‐life. These findings, showing direct activation by RA of RARα gene transcription in human neuroblastoma cells, suggest differences in the overall regulation of this receptor from that found in most other RA‐inducible tissue.