Glucocorticoids differentially inhibit expression of the RET proto-oncogene

Amanda Capes-Davis, Scott D. Andrew, Valentine J. Hyland, Stephen Twigg, Diana L. Learoyd, Trisha Dwight, Debbie J. Marsh, Bruce G. Robinson

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


The RET proto-oncogene encodes a receptor tyrosine kinase activated by the binding of factors from the glial cell line-derived neurotrophic factor (GDNF) family to receptor-α components such as GDNF family receptor α-1 (GFRα-1). Mutations within the sequence of the RET proto-oncogene are associated with multiple endocrine neoplasia type 2 (MEN 2), an inherited tumor syndrome characterized by the development of medullary thyroid carcinoma (MTC) and other neuroendocrine tumors. Despite Northern analysis showing that RET is expressed in the majority of MTCs, the factors regulating this expression are poorly understood. To address this issue we examined RET expression in response to glucocorticoids in the TT cell line, derived from a metastatic MTC. The synthetic glucocorticoid dexamethasone was found to reduce RET expression at both mRNA and protein levels. This effect was dose responsive and maximal at 24 h. The reduction in RET mRNA was shown to be specific to glucocorticoids and was also seen in a primary MTC culture. Nuclear run-on studies revealed the reduction in steady-state RNA to be due to a decrease in RET mRNA transcription and the effect was shown to be independent of new protein synthesis or RNA stability. Dexamethasone was also found to exert an inhibitory effect upon cell growth, suggesting a potential use for glucocorticoids in the treatment of medullary carcinoma and MEN 2.

Original languageEnglish
Pages (from-to)311-326
Number of pages16
JournalGene Expression
Issue number5-6
Publication statusPublished - 1999


Dive into the research topics of 'Glucocorticoids differentially inhibit expression of the RET proto-oncogene'. Together they form a unique fingerprint.

Cite this