Rapid induction of the c-jun protooncogene in the avian oviduct by the antiestrogen tamoxifen.

Abstract

This report describes a rapid regulation of the expression of the c-jun protooncogene by the antiestrogen tamoxifen (Tam). The c-jun protooncogene codes for an important component of the AP-1 transcription factor complex, which regulates the expression of many unlinked genes. Repeated experiments have shown that Tam rapidly increases the steady-state c-jun mRNA levels in the avian oviduct but decreases the levels in the liver. The Tam effects are time- and dose-dependent. These results are supported by other studies that have demonstrated that 17 beta-estradiol decreases steady-state levels of c-jun protooncogene mRNA in oviducts of animals fully withdrawn from estradiol. The effect of Tam in the avian oviduct is in contrast to the reported effects of Tam on the expression of practically all other genes in the avian oviduct and other animal tissues. Transcription analyses using nuclear runoff experiments with oviduct nuclei demonstrate a decrease in the c-jun gene transcription within minutes after Tam treatment with a return to 75% of control values by 4 hr. The fact that Tam transiently decreases the transcription of the c-jun gene but increases the steady-state c-jun mRNA levels suggests that Tam must alter both transcriptional and post-transcriptional events. The results support a role of the c-jun protooncogene as a regulatory gene in the cascade model for steroid action whereby steroids rapidly regulate the regulatory genes, which in turn regulate many other structural genes.

Clinical Pharmacokinetics of Endocrine Agents Used in Advanced Breast Cancer

“…The drug is thought to act by blocking estrogen stimulation of breast cancer growth, mimicking the first step of estrogen action, the promotion of both translocation and nuclear binding of the estrogen 331 receptor (Borgna & Rochefort 1981;Jordan et al 1977). The basis of the antagonism may be that tamoxifen alters transcriptional and post-transcriptional events (Lau et al 1991;Webster et al 1988).…”

Synergistic effect of tamoxifen and phorbol ester TPA on retrovirus synthesis in a human mammary carcinoma cell line

“…The mechanism of the observed synergy in ER-cells remains to be demonstrated. It is conceivable that different responsive elements may act cooperatively to stimulate viral transcription, or members of the signal transduction cascade like jun (Lau et al, 1991) may be simultaneously changed by TPA or TAM. The putative tumour-promoting activity (Dragun et al, 1991) and the strong hepatocarcinogenic effect of TAM (Williams et al, 1993) may also play a role.…”

From Reptilian Phylogenomics to Reptilian Genomes: Analyses of c-<i>Jun</i> and <i>DJ-1</i> Proto-Oncogenes

“…However, regulation of c-Jun by an ERE in the coding region could be a derived character state of a group less inclusive than all amniotes, whether this less inclusive group is the mammals, the rodent-primate clade (Euarchontoglires) [see Murphy et al, 2001], rodents, or even a subset of rodents. Estrogen regulation of chicken c-Jun involves transcriptional and post-transcriptional mechanisms [Lau et al, 1991] and estrogen induction of c-Jun in human endometrial fibroblasts and cancer cell lines requires protein kinase C [Fujimoto et al, 1996]. Thus, estrogen regulation of c-Jun requires more than ER binding to an ERE in some systems.…”