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Expression of co-factors (SMRT and Trip-1) for retinoic acid receptors in human neuroectodermal cell lines
S Bernardini1, G Melino, F Saura
1Post Graduate School in Biochemistry and Clinical Chemistry, University of Camerino, Rome, Italy.
Abstract:
Retinoic acid (RA) induces growth inhibition, differentiation or cell death in many human neuroblastoma cell lines. Recently, the transactivation activity of nuclear retinoids receptors has been shown to be modulated through physical association with other proteins that act as co-activators or as co-repressors. We investigated the expression of the co-repressor (SMRT) and co-activator (Trip 1) for retinoid and thyroid-hormone receptors in several neuroectodermal tumour cell lines, and its modulation by all-trans-retinoic acid, as well as by synthetic agonists, for RAR alpha, RAR beta, RAR gamma and RXR. We demonstrate that (i) SMRT and Trip-1 mRNAs are expressed in many human neuroblastoma and melanoma cell lines in basal conditions, (ii) SMRT mRNA expression in human neuroblastoma cell line SK-N-BE(2) increases after 48 hours of incubation with 1 microM RA and RARs specific agonists, (iii) Trip-1 mRNA in the same cell line does not change during incubation with RA or selective synthetic agonists for RARs and RXR.
Insights
Retinoic acid (RA) affects neuroblastoma cells by modulating co-repressor and co-activator expression. SMRT mRNA levels increase with RA treatment, while Trip-1 mRNA remains unchanged, impacting retinoid signaling in these tumors.
Area of Science:
- Molecular Biology
- Cancer Research
- Neuro-oncology
Background:
- Retinoic acid (RA) is known to induce growth inhibition, differentiation, or cell death in human neuroblastoma.
- Nuclear retinoid receptors' transactivation activity is modulated by co-activators and co-repressors.
- Understanding these interactions is crucial for neuroblastoma treatment strategies.
Purpose of the Study:
- To investigate the expression of SMRT (co-repressor) and Trip 1 (co-activator) in neuroectodermal tumor cell lines.
- To determine how all-trans-retinoic acid (RA) and synthetic agonists modulate SMRT and Trip 1 expression.
- To explore the role of these co-regulators in retinoid signaling pathways relevant to neuroblastoma.
Main Methods:
- Analysis of SMRT and Trip 1 mRNA expression in neuroblastoma and melanoma cell lines.
- Treatment of SK-N-BE(2) neuroblastoma cells with RA and specific agonists for RARs (RAR alpha, RAR beta, RAR gamma) and RXR.
- Quantitative assessment of mRNA level changes using RT-PCR or similar techniques.
Main Results:
- SMRT and Trip 1 mRNAs are constitutively expressed in various human neuroblastoma and melanoma cell lines.
- Incubation with RA or RAR-specific agonists significantly increased SMRT mRNA expression in the SK-N-BE(2) cell line after 48 hours.
- Trip 1 mRNA levels in the SK-N-BE(2) cell line showed no significant change upon treatment with RA or selective synthetic agonists for RARs and RXR.
Conclusions:
- SMRT and Trip 1 are expressed in neuroectodermal tumor cell lines and are differentially regulated by retinoids.
- RA and its agonists upregulate SMRT expression, suggesting a role for co-repressor modulation in retinoid-induced effects on neuroblastoma.
- The lack of change in Trip 1 expression indicates a selective impact on co-regulator pathways, potentially offering therapeutic targets.