Post-transcriptional control of myc and p53 expression during differentiation of the embryonal carcinoma cell line F9 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1985-10

AUTHORS

Carola Dony, Michael Kessel, Peter Gruss

ABSTRACT

Teratocarcinoma cells provide us with a model system for the study of differentiation and development1–3. One of the best characterized cell lines, the embryonal carcinoma stem cell line F9, differentiates after treatment with retinoic acid (RA) and dibutyryl cyclic AMP into parietal endoderm4. This differentiation process is accompanied by the induction of several genes, for example, those encoding collagen IV, plasminogen activator and intermediate filaments like laminin4–6. In contrast, a marked reduction of stable messenger RNA has been observed for the gene encoding p53 and for c-myc7,8. Both cellular oncogenes seem to be involved in the regulation of cellular proliferation and neoplastic transformation8–12. For growth-arrested 3T3 fibroblasts, growth-factor-induced changes of myc RNA are controlled at the level of transcription13. In contrast, F9 cells provide a differentiation system in which cells are able to change from a tumorigenic state into non-dividing, non-tumorigenic endodermal cells5. The latter process enabled us to study the regulation of myc and p53 genes in the same cells at different stages of growth, tumorigenicity and differentiation. Here we report that down-regulation of stable myc and p53 RNA during irreversible differentiation of F9 cells occurs at the post-transcriptional level. Using an in vitro nuclear transcription assay14, we found that the polymerase II density on both genes remains constant during differentiation. In agreement with this interpretation, we detected myc RNA as stable transcripts in differentiated F9 cells after treatment of the cells with cyclo-heximide. The post-transcriptional regulatory mechanisms controlling p53 and myc stability follow different kinetics. Whereas the down-regulation of myc seems to be an early event of F9 differentiation occurring within the first 24 h, the post-transcriptional regulation of p53 occurs at a later stage (two to three days), possibly as a consequence of cell cycle changes. More... »

PAGES

636-639

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/317636a0

DOI

http://dx.doi.org/10.1038/317636a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026380783

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/2414665


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