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Nucleic Acids Research, 1990, Vol. 18, No. 5 1153-1157
© 1990

MOLECULAR BIOLOGY

Post-transcriptional control of c-myc proto-oncogene expression by glucocorticoid hormones in human T lymphoblastic leukemic cells

M. Maroder, S. Martinotti1, A. Vacca, I. Screpanti, E. Petrangeli, L. Frati and A. Gulino1

Department of Experimental Medicine, University La Sapienza 324 viale Regina Elena, 00161 Roma 1Department of Experimental Medicine, University of L'Aquila Collemaggio, L'Aquila, Italy

Received December 12, 1989. Revised February 1, 1990. Accepted February 1, 1990.

We have studied the regulation of the human c-myc proto-oncogene by glucocorticoid hormones in T lymbhoblastic leukemic cells. A significant decrease (50%) of the steady state levels of c-myc mRNA was observed as early as 3 h after dexamethasone treatment of CEM-1.3 human tymphoma cells, reaching less than 5% values, with respect to untreated cells, 24 h after hormone administration. Nuclear run-on experiments showed no modifications of the transcriptional rate from the first exon. However, a slight decrease (15%) of the transcript elongation from the first exon/first intron boundary was observed In the dexamethasone-treated cells. Using actinomycin D to block gene transcription, we have observed a significant increase in the rate of c-myc RNA specific decay after dexamethasone treatment. Furthermore, cycloheximide was able to overcome completely the dexamethasone-induced down-regulation of the c-myc gene expression. Our data suggest that dexamethasone is able to inhibit human c-myc gene expression primarily at the post-transcriptional level, through the synthesis of hormone-induced regulatory protein(s) controlling c-myc transcript stability.


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