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Rapid inhibition of the c-jun proto-oncogene expression in avian oviduct by estrogen
C K Lau1, M Subramaniam, K Rasmussen
1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905.
Abstract:
The c-jun proto-oncogene codes for an important component of the AP-1 transcription factor complex which regulates the expression of many genes. This paper demonstrates that the steady state c-jun mRNA level in the avian oviduct is markedly decreased to 50% of control values within 30 minutes after estrogen injection into the animals. In the avian liver, the level is rapidly increased over 10 fold. Nuclear run-off transcription analysis demonstrates that the decrease in the c-jun mRNA levels in the avian oviduct occurs at least in part at the level of transcription. These changes are reproducible in repeat experiments. This response in the avian oviduct is unique since 1) it is the first demonstration of a steroid effect on c-jun expression in any animal system, 2) the changes in c-jun mRNA occur much more rapidly than most steroid responsive genes, and 3) it is the rare demonstration of an estrogen inhibition of the expression of a gene. A role for the c-jun proto-oncogene as an early regulatory gene in the cascade model for steroid action is proposed.
Insights
Estrogen rapidly alters c-jun proto-oncogene expression in birds. Oviduct levels decrease, while liver levels increase, suggesting a role in steroid hormone action.
Area of Science:
- Molecular Biology
- Endocrinology
- Gene Regulation
Background:
- The c-jun proto-oncogene is a key component of the AP-1 transcription factor, regulating numerous genes.
- Steroid hormones influence gene expression through complex regulatory pathways.
Purpose of the Study:
- To investigate the effect of estrogen on c-jun proto-oncogene expression in the avian oviduct and liver.
- To determine the mechanism and kinetics of estrogen-induced c-jun mRNA changes.
Main Methods:
- Administration of estrogen to avian subjects.
- Measurement of c-jun mRNA levels in oviduct and liver tissues.
- Nuclear run-off transcription assays to assess transcriptional regulation.
Main Results:
- Estrogen injection rapidly decreased c-jun mRNA levels by 50% in the avian oviduct within 30 minutes.
- Estrogen injection rapidly increased c-jun mRNA levels over 10-fold in the avian liver.
- Nuclear run-off assays indicated that the decrease in oviduct c-jun mRNA occurred, at least partly, at the transcriptional level.
Conclusions:
- This study presents the first evidence of a steroid hormone effect on c-jun expression in any animal system.
- The rapid changes in c-jun mRNA levels in response to estrogen are faster than most known steroid-responsive genes.
- Estrogen's inhibitory effect on c-jun expression in the oviduct is a rare observation, proposing c-jun as an early regulatory gene in steroid action models.