Estrogen regulates expression of the jun family of protooncogenes in the uterus

doi:10.1016/0960-0760(92)90037-J

The Journal of Steroid Biochemistry and Molecular Biology

Volume 41, Issue 2, February 1992, Pages 113-123

https://doi.org/10.1016/0960-0760(92)90037-J Get rights and content

Abstract

Treatment of immature female rats with estradiol increases uterine levels of c-jun and jun-B mRNAs approx. 10-fold. This effect is specific for estrogenic steroids. The induction of jun transcripts is blocked by actinomycin D but not puromycin, suggesting that the hormonal effect is due at least in part to transcriptional activation. The hormone effect is rapid and peak levels of jun mRNAs are seen within 3 h after treatment. Inductions of jun and fos transcripts in the uterus by estradiol exhibit similar dose response curves (maximum responses at 4 μg/kg). Estradiol also elevates uterine levels of jun-D, and this induction is insensitive to puromycin. In vivo treatment with the phorbol ester TPA rapidly elevates uterine levels of fos, jun, and myc transcripts, indicating that expression of these photooncogenes is under non-estrogenic as well as estrogenic regulation in this target tissue. These results suggest that multiple members of the jun and fos protooncogene families may play a role in amplifying the uterine response to estrogens.

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The rodent uterus is a widely studied target tissue for sexual steroid hormone action. The aim of the present study was to assess the molecular mechanism that participates in the initiation of cell proliferation of the rat uterine epithelial cells during the estrus (E)–metestrus (M) transition. Cell proliferation, ERα, c-fos, cyclin D1 and D3, cdk4, and cdk6 proteins were assessed in these animals by immunohistochemistry. Estradiol (E₂) and progesterone (P₄) plasma levels were assessed by RIA. The results indicate that the glandular epithelium starts to proliferate at 21:00 h on estrus day, and initiates at least 3 h before the luminal epithelium does. Fos expression was markedly increased during the afternoon of estrus day, and its increase was in parallel to ERα expression. Interestingly, both, cyclin D1 and D3 were abundantly expressed in the luminal and glandular epithelia, and nuclear immunolabelling of cyclin D1 and D3 precedes BrdU incorporation in the cell. cdk4 and cdk6 were localized in the nuclei in both epithelia throughout the studied time course. In addition, cdk4 was more abundant throughout estrus and metestrus days than cdk6. The overall results indicate that ERα, Fos and cyclins D1 and D3, cdk4 and cdk6 are expressed in both glandular and luminal epithelia of the rat uterus during the E–M transition. In conclusion, there is a good correlation between sequential expression of these proteins and cell cycle progression in the rat uterine epithelial cells during the estrous cycle. However, the differences observed in the cellular localization, time course of expression and the cellular types that express both cyclins between physiological and pharmacological conditions, demonstrated different mechanisms of regulation and should be due to the complex hormonal milieu during the estrous cycle.
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Estrogen regulates expression of the jun family of protooncogenes in the uterus

Abstract

Biochim. Biophys. Acta

Trends Biochem. Sci.

Cell

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Cell

Cell

Cell

FEBS Lett.

J. Biol. Chem.

Cell

Cell

Cell

Cell

Cell

Cell

Effect of estrogen on mitosis in individual cell types of the immature rat uterus

Biol. Reprod.

Nuclear Proto-Oncogenes FOS and JUN

A. Rev. Cell Biol.

Regulation of c-MYC and C-FOS expression by animal cell growth factors

In Vitro Cell. Dev. Biol.

The fos oncogene

Transient induction of c-fos and c-myc is an immediate consequence of growth factor stimulation

Cancer Surv.

Estrogen regulation of c-fos messenger ribonucleic acid

Molec. Endocr.

Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus

Molec. Endocr.

Fos-associated protein p39 is the product of the jun protooncogene

Science

Leucine repeats and an adjacent DNA binding domain mediate the formation of function cFos-cJun heterodimers

Science

Both Jun and Fos contribute to transcription activation by the heterodimer

Oncogene