Transcriptional activation of heat shock protein 27 gene expression by 17beta-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists

Porter, Weston W.; Wang, F; Duan, Renqin; Qin, Chunhua; Castro-Rivera, Emely; Kim, Kyounghyun; Safe, Stephen

doi:10.1677/jme.0.0260031

Cited by 60 publications

(41 citation statements)

References 78 publications

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“…When cells were cotreated with 17β-estradiol (E2) and TCDD, AhR activated by TCDD binds to this composite site and prevents the DNA binding of the ER/ Sp1 complex, resulting in the inhibition of E2-dependent transactivation of the cathepsin D gene 25) . The same process was also demonstrated in the other estrogen-inducible gene promoters, pS2 (a cell-proliferation related gene) 26) , c-fos 27) and hsp 27 28) .…”

Section: Mechanisms Underlying Diversity Of Hormonal Actionssupporting

confidence: 58%

Gene Expression Assay for Hazard Assessment of Chemicals.

Otsuka

2002

INDUSTRIAL HEALTH

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Recent progress in our knowledge of gene expression systems provides evidence that many industrial chemicals affect the transcriptional machineries directly or indirectly, and gene expression is now recognized as one of the main targets of many chemicals. In view of the increasing number of man-made chemicals, it is therefore necessary to establish a reliable gene expression assay with rapidity and high sensitivity. Among various gene expression assays, the so-called reporter assay is now accepted as a suitable tool to assess hazardous effects of chemicals on gene expression. This article focuses on the principle and applications of the reporter assay in research on endocrine disrupters.

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Section: Mechanisms Underlying Diversity Of Hormonal Actionssupporting

confidence: 58%

Gene Expression Assay for Hazard Assessment of Chemicals.

Otsuka

2002

INDUSTRIAL HEALTH

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“…TCDD inhibits transactivation of several E-induced genes in breast cancer cells (9,14,18,21,25,38), and different mechanisms of inhibitory AhR-ER cross talk have been proposed (36,44). The results summarized in Fig.…”

Section: Resultsmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor Mediates Degradation of Estrogen Receptor α through Activation of Proteasomes

Wormke¹,

Stoner²,

Saville³

et al. 2003

Molecular and Cellular Biology

276

196

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress 17␤-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D, and MCF-7 human breast cancer cells with TCDD induces proteasomedependent degradation of endogenous estrogen receptor ␣ (ER␣).The proteasome inhibitors MG132, PSI, and PSII inhibit the proteasome-dependent effects induced by TCDD, whereas the protease inhibitors EST, calpain inhibitor II, and chloroquine do not affect this response. ER␣ levels in the mouse uterus and breast cancer cells were significantly lower after cotreatment with E plus TCDD than after treatment with E or TCDD alone, and our results indicate that AhR-mediated inhibition of E-induced transactivation is mainly due to limiting levels of ER␣ in cells cotreated with E plus TCDD. TCDD alone or in combination with E increases formation of ubiquitinated forms of ER␣, and both coimmunoprecipitation and mammalian two-hybrid assays demonstrate that TCDD induces interaction of the AhR with ER␣ in the presence or absence of E. In contrast, E does not induce AhR-ER␣ interactions. Thus, inhibitory AhR-ER␣ cross talk is linked to a novel pathway for degradation of ER␣ in which TCDD initially induces formation of a nuclear AhR complex which coordinately recruits ER␣ and the proteasome complex, resulting in degradation of both receptors.Estrogenic hormones induce their tissue-specific responses through binding the estrogen receptor (ER), which is a ligandactivated transcription factor and a member of the nuclear receptor (NR) superfamily (3, 15). The two ER subtypes (ER␣ and ER␤) and other NRs exhibit modular structures containing N-terminal activation function 1 (AF1) and C-terminal AF2, which also contains the ligand-binding domain, a DNAbinding domain (DBD), and an adjacent hinge region. Most early-stage mammary tumors are ER positive and are responsive to endocrine therapies which target ER␣ and/or E biosynthesis (5, 13, 47). Selective ER modulators, such as tamoxifen, are extensively used for treating early-stage breast cancer, and the primary modes of action of selective ER modulators involve competitive binding to the ER and subsequent inhibition of one or more steps in ER-mediated transactivation. Several studies show that there are important mechanistic differences among antiestrogens, and this is consistent with their tissuespecific ER antagonist-agonist activities (20,52,53). For example, the "pure" antiestrogens ICI 164,384 and/or ICI 182,780 not only bind ER␣ with high affinity but induce a rapid proteasome-dependent degradation of the receptor, and this is observed in breast cancer cells and human tumors (41, 52). Rapid degradation of ER␣ protein in cells or tumors treated with ICI 164,384 or 182,780 may play an important role in the antiestrogenic activity of these compounds.Studies in this laboratory have investigated inhibition of ER signaling through cross talk with the ligand-activated aryl hydrocarbon rece...

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“…In addition, it is well known that E2 can induce c-Myc through transcriptional activation (38) and also that c-Myc is an activator of telomerase (27,39). We therefore analyzed c-Myc induction by both E2 and TCDD treatment and, as shown by Western blotting, a significant increase in c-Myc protein levels was indeed induced by E2 and TCDD (Fig.…”

Section: Discussionmentioning

confidence: 99%

Activation of telomerase in BeWo cells by estrogen and 2,3,7,8-tetrachlorodibenzo-p-dioxin in co-operation with c-Myc

Sarkar

Shiizaki²,

Yonemoto³

et al. 2006

Int J Oncol

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Abstract. Telomerase activation, known to be stimulated by estrogen, is essential for cellular immortalization and transformation, both of which play a role in tumorigenesis. Dioxin and dioxin-like compounds have been shown to induce endometriosis and promote estrogen-dependent tumors. In this study, we show that either 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) or a combination of TCDD and 17-ß estradiol (E2) increase telomerase activity and the expression of the human telomerase catalytic subunit (hTERT) in human choriocarcinoma (BeWo) cells. Compared with estrogen or TCDD alone, the combination treatment did not show an additive effect. Likewise, treatment with either E2 or TCDD increased DNA synthesis and the cell population in S-phase, as detected by FACS analysis. However, following treatment with the E2 and TCDD combination, the proportion of cells in S-phase was actually lower than in cells treated with TCDD alone. These results suggest that TCDD alone mimics estrogenic action in telomerase activation and cell proliferation but, in the presence of estrogen, TCDD-induced actions were partially counteracted. E2 and TCDD also induced c-Myc, which is a transcriptional activator of hTERT in BeWo, but neither of these agents induced telomerase activity in HO15.19 c-myc-null cells. In contrast, only TCDD upregulated telomerase in TGR-1 cells, which are c-Myc expressing but lacking ER expression. The findings suggest that TCDD induces telomerase activity mediated through AhR signaling and/or ER-independent c-Myc signaling. The present study provides insight into the mechanism of promoter activity of TCDD in estrogen-related tumors.

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Transcriptional activation of heat shock protein 27 gene expression by 17beta-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists

Cited by 60 publications

References 78 publications

Gene Expression Assay for Hazard Assessment of Chemicals.

Gene Expression Assay for Hazard Assessment of Chemicals.

The Aryl Hydrocarbon Receptor Mediates Degradation of Estrogen Receptor α through Activation of Proteasomes

Activation of telomerase in BeWo cells by estrogen and 2,3,7,8-tetrachlorodibenzo-p-dioxin in co-operation with c-Myc

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