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Mechanism of action of retinoids
Abstract:
In several recent reviews, we have suggested that the mechanism of action of retinoids in controlling cell differentiation is related to their effects on the expression of oncogenes and peptide growth factors. It is currently believed that oncogenes control metabolic pathways that involve peptide growth factors and their receptors, as well as postreceptor signaling mechanisms. Retinoids, therefore, have been valuable probes to study the function of oncogenes and peptide growth factors. In several tumor cells, including human promyelocytic leukemia, human and murine neuroblastoma, and murine teratocarcinoma, retinoic acid induces terminal differentiation, accompanied by suppression of the expression of either the c-myc or the N-myc gene. Many studies have indicated that retinoic acid can markedly increase the number of cellular receptors for epidermal growth factor, which is partially encoded by another oncogene, erb-B. We have shown that retinoic acid greatly inhibits the anchorage-independent growth of a rat fibroblast cell line that has been transfected with the c-myc gene, particularly when these cells are stimulated by the combination of platelet-derived growth factor and transforming growth factor-beta. At present, the mechanisms by which retinoids control oncogene and growth factor expression are unknown. A wide range of new compounds, including the retinoidal benzoic acid derivatives, are now available to study these mechanisms, and will necessitate the identification of a high-affinity receptor for retinoids and the elucidation of the interaction of this receptor with the genome of the cell. The recent synthesis of new terephthalic acid anilides and chalcone carboxylic acid derivatives, which have retinoid-like activity, offers a particularly useful approach to this problem.
Insights
Retinoids control cell differentiation by affecting oncogene and growth factor expression. New retinoid compounds aid in studying these mechanisms and identifying retinoid receptors.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Retinoids influence cell differentiation via oncogene and peptide growth factor expression.
- Oncogenes regulate pathways involving growth factors, their receptors, and signaling.
- Retinoids serve as tools to investigate oncogene and growth factor functions.
Purpose of the Study:
- To explore the role of retinoids in controlling cell differentiation.
- To understand the relationship between retinoids, oncogenes, and growth factors.
- To investigate novel retinoid compounds for studying these mechanisms.
Main Methods:
- Examining retinoic acid's effect on differentiation in tumor cells (leukemia, neuroblastoma, teratocarcinoma).
- Assessing changes in oncogene expression (c-myc, N-myc) and growth factor receptors (epidermal growth factor).
- Evaluating retinoid inhibition of anchorage-independent growth in transfected fibroblast cell lines.
Main Results:
- Retinoic acid induces terminal differentiation and suppresses c-myc or N-myc gene expression in tumor cells.
- Retinoic acid increases cellular receptors for epidermal growth factor.
- Retinoic acid inhibits anchorage-independent growth, especially with growth factor stimulation.
Conclusions:
- Retinoids modulate cell differentiation through oncogene and growth factor pathways.
- The precise mechanisms of retinoid control over oncogene and growth factor expression require further elucidation.
- New synthetic retinoid derivatives offer promising avenues for receptor identification and genomic interaction studies.