GC-rich promoter elements maximally confers estrogen-induced transactivation of LRP16 gene through ERα/Sp1 interaction in MCF-7 cells

Han, Wei; Ling, Yi He; Zhao, Yang; Li, Qi; Wu, Zhaojun; Hao, Hao Jie; Song, Hai Jing

doi:10.1016/j.jsbmb.2007.12.009

Cited by 14 publications

(16 citation statements)

References 42 publications

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“…The ligand-independent ERα activity was increased by phosphorylation at specific serine residues in the N-terminal domain as activated by the growth factor pathway (37,38). Furthermore, ERα is known to interact with other transcription factors, such as Sp1 and AP-1, and it may use the constitutive transcriptional function of these factors (39,40). Thus, unliganded ERα may play a role in regulating basal Kiss1 transcription in the ARC.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain

Tomikawa¹,

Uenoyama²,

Ozawa³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

132

118

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This study aims to determine the epigenetic mechanism regulating Kiss1 gene expression in the anteroventral periventricular nucleus (AVPV) to understand the mechanism underlying estrogen-positive feedback action on gonadotropin-releasing hormone/gonadotropin surge. We investigated estrogen regulation of the epigenetic status of the mouse AVPV Kiss1 gene locus in comparison with the arcuate nucleus (ARC), in which Kiss1 expression is down-regulated by estrogen. Histone of AVPV Kiss1 promoter region was highly acetylated, and estrogen receptor α was highly recruited at the region by estrogen. In contrast, the histone of ARC Kiss1 promoter region was deacetylated by estrogen. Inhibition of histone deacetylation upregulated in vitro Kiss1 expression in a hypothalamic non-Kiss1-expressing cell line. Gene conformation analysis indicated that estrogen induced formation of a chromatin loop between Kiss1 promoter and the 3′ intergenic region, suggesting that the intergenic region serves to enhance estrogen-dependent Kiss1 expression in the AVPV. This notion was proved, because transgenic reporter mice with a complete Kiss1 locus sequence showed kisspeptin neuronspecific GFP expression in both the AVPV and ARC, but the deletion of the 3′ region resulted in greatly reduced GFP expression only in the AVPV. Taken together, these results demonstrate that estrogen induces recruitment of estrogen receptor α and histone acetylation in the Kiss1 promoter region of the AVPV and consequently enhances chromatin loop formation of Kiss1 promoter and Kiss1 gene enhancer, resulting in an increase in AVPV-specific Kiss1 gene expression. These results indicate that epigenetic regulation of the Kiss1 gene is involved in estrogen-positive feedback to generate the gonadotropin-releasing hormone/gonadotropin surge.

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Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain

Tomikawa¹,

Uenoyama²,

Ozawa³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

132

118

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“…The differential induction of LRP16 expression by liganded and unliganded ERa in SKOV3 cells revealed a completely different regulatory mechanism compared with that in estrogen-sensitive cancer cells. A proximal region of K676 to K24 bp of the human LRP16 promoter was previously identified to be essential for estrogen induction of LRP16 expression in MCF-7 cells (Han et al 2008). Estrogen induces LRP16 gene transactivation by stimulating the interaction and recruitment of ERa and Sp1 transcription factor at a 1/2 ERE/ GC-rich site and multiple GC-rich sites present in K676 to K24 bp of the upstream regulatory region of LRP16 gene (Zhao et al 2005, Han et al 2008.…”

Section: Discussionmentioning

confidence: 99%

“…A proximal region of K676 to K24 bp of the human LRP16 promoter was previously identified to be essential for estrogen induction of LRP16 expression in MCF-7 cells (Han et al 2008). Estrogen induces LRP16 gene transactivation by stimulating the interaction and recruitment of ERa and Sp1 transcription factor at a 1/2 ERE/ GC-rich site and multiple GC-rich sites present in K676 to K24 bp of the upstream regulatory region of LRP16 gene (Zhao et al 2005, Han et al 2008. By promoter analysis, we demonstrate that the fragment from K676 to K214 bp of the LRP16 upstream regulatory region mainly confers estrogen-repressed effect of LRP16 expression (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Mammalian expression plasmid for ERa (pS5G-hERa) was provided by Prof. Hajime Nawata at Kyushu University, and the reporter 3!ERE-TATA-Luc was provided by Prof. Donald P McDonnell at Duke University Medical Center (Norris et al 1998). The luciferase reporter constructs pGL3-S 0 , pGL3-S 2 , pGL3-S 4 , pGL3-S 5 , and pGL3-S B1 , containing the fragment of K2623 to K24 bp, K1775 to K24 bp, K1064 to K24 bp, K676 to K24 bp, K213 to K24 bp of the LRP16 upstream regulatory region respectively, have been previously described (Zhao et al 2005, Han et al 2008.…”

Section: Plasmidsmentioning

confidence: 99%

“…In cell culture, it has been shown that the expression level of LRP16 is strongly dependent on the estrogen actions in ERa-positive breast and endometrial cancer cell lines . A proximal region of K676 to K24 bp of the human LRP16 promoter, in which a 1/2 ERE/Sp1 site and multiple GC-rich elements that confer estrogen responsiveness have been recognized, is essential for estrogen action (Zhao et al 2005, Han et al 2008. Interestingly, estrogen-upregulated LRP16 can interact with ERa and enhance the receptor's transcriptional activity in a ligand-dependent manner, thus establishing a positive feedback regulatory loop between LRP16 and ERa signal transduction in estrogen-responsive breast cancer cells .…”

Section: Introductionmentioning

confidence: 99%

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Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

Tian

Wu²,

Zhao³

et al. 2009

Journal of Endocrinology

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Previously, we investigated the induction effect of LRP16 expression by estrogen (17b-estradiol, E 2 ) and established a feed-forward mechanism that activated estrogen receptor a (ERa) transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ERa signaling transduction by functioning as an ERa coactivator. In this study, we demonstrated that LRP16 expression was upregulated in E 2 -responsive BG-1 ovarian cancer cells, but was downregulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The unliganded ERa upregulated LRP16 expression and enhanced LRP16 promoter activity in SKOV3 cells; however, this induction was blocked by estrogen stimulation. Results from chromatin immunoprecipitation experiment revealed a strong recruitment of the unliganded ERa at LRP16 promoter in the absence of estrogen; however, ERa was largely released from the DNA upon E 2 stimulation. Modulation in LRP16 expression level did not significantly change the proliferation rate of SKOV3 cells and the growth responsiveness of cells to E 2 . Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated estrogen response elementdependent ERa reporter gene activity and E 2 -induced c-Myc expression. Our study suggests a novel mechanism of estrogen resistance of ovarian cancer by which estrogenrepressed signaling pathway antagonizes estrogen-activated signaling transduction.

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Estrogen and its receptors in cancer

Chen

Zeng

Tse

2008

Medicinal Research Reviews

185

134

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The involvement of estrogen and its receptors in the development of cancer has been known for years. However, the exact mechanism responsible is far from clear. The estrogen-mediated carcinogenic process is complicated by recent findings, which reveal that estrogens have multiple functions in cells, which can be either adverse or beneficial, and that the effects of estrogen may be cell-type or organ dependent. The estrogenic effect may be also greatly influenced by the state of two estrogen receptors, ERalpha and ERbeta. This review will discuss the role and function of estrogens and its receptors in cancers of three categories: (1) Breast cancer and gynecologic cancers, (2) Cancers of endocrine organs, (3) Lung cancer and cancers of digestive system. We will also review some novel treatments aiming to interfere with relevant pathways mediated by estrogens and its receptors.

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GC-rich promoter elements maximally confers estrogen-induced transactivation of LRP16 gene through ERα/Sp1 interaction in MCF-7 cells

Cited by 14 publications

References 42 publications

Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain

Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain

Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

Estrogen and its receptors in cancer

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