Estrogens promote proliferation of the seminoma-like TCam-2 cell line through a GPER-dependent ERα36 induction

Background: is an oncomiR in human hepatocellular carcinoma and is highly expressed in liver, but its regulation is uncharacterized. Results: Dehydroepiandrosterone (DHEA) rapidly increases miR-21 transcription in HepG2 cells by activating G-proteincoupled estrogen receptor (GPER). Conclusion: miR-21 transcription is regulated by DHEA through GPER. Significance: GPER may be among the activators of miR-21 expression in human hepatocellular carcinoma.

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“…As positive controls, E 2 and DHT increased ER␣36 in HepG2 cells (Fig. 4B), similar to findings in TCam-2 seminoma cells (40).…”

Section: Gper/gpr30 Activation Increases Mir-21supporting

confidence: 85%

Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells

Teng

Radde

Litchfield

et al. 2015

Journal of Biological Chemistry

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“…JAK2/STAT3 signaling was also reported to be involved in GPER signaling in the hypothalamus and SKBR-3 breast cancer cells [45, 46]. EGFR mRNA expression was not affected by ERα36 overexpression in normal epithelial cells (data not shown) whereas a positive cross-activation of both gene expression has been reported in seminoma and breast cancer cells [16, 41, 42]. Since EGF is present in cell culture medium, ERα36 protein could enhance a basal level of EGFR signaling through PI3K/AKT and STAT3/5.…”

Section: Discussionmentioning

confidence: 96%

“…Indeed, GPER mRNA expression was stimulated by 2.09 fold in MCF-10A cells overexpressing ERα36. Moreover, ERα36 was shown to interact physically with GPER [41, 42] and/or to collaborate with GPER to trigger downstream signaling in female reproductive tract, seminoma or breast cancer cells [5, 16, 17, 43, 44]. JAK2/STAT3 signaling was also reported to be involved in GPER signaling in the hypothalamus and SKBR-3 breast cancer cells [45, 46].…”

Section: Discussionmentioning

confidence: 99%

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Mammary epithelial cell phenotype disruption in vitro and in vivo through ERalpha36 overexpression

Thiébaut¹,

Chamard-Jovenin²,

Chesnel³

et al. 2017

PLoS ONE

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Estrogen receptor alpha 36 (ERα36) is a variant of the canonical estrogen receptor alpha (ERα66), widely expressed in hormone sensitive cancer cells and whose high expression level correlates with a poor survival prognosis for breast cancer patients. While ERα36 activity have been related to breast cancer progression or acquired resistance to treatment, expression level and location of ERα36 are poorly documented in the normal mammary gland. Therefore, we explored the consequences of a ERα36 overexpression in vitro in MCF-10A normal mammary epithelial cells and in vivo in a unique model of MMTV-ERα36 transgenic mouse strain wherein ERα36 mRNA was specifically expressed in the mammary gland. By a combination of bioinformatics and computational analyses of microarray data, we identified hierarchical gene networks, downstream of ERα36 and modulated by the JAK2/STAT3 signaling pathway. Concomitantly, ERα36 overexpression lowered proliferation rate but enhanced migration potential and resistance to staurosporin-induced apoptosis of the MCF-10A cell line. In vivo, ERα36 expression led to duct epithelium thinning and disruption in adult but not in prepubescent mouse mammary gland. These phenotypes correlated with a loss of E-cadherin expression. Here, we show that an enhanced expression of ERα36 is sufficient, by itself, to disrupt normal breast epithelial phenotype in vivo and in vitro through a dominant-positive effect on nongenomic estrogen signaling pathways. These results also suggest that, in the presence of adult endogenous steroid levels, ERα36 overexpression in vivo contributes to alter mammary gland architecture which may support pre-neoplastic lesion and augment breast cancer risk.

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“…Kang et al found that G1, a GPER-specific agonist, could stimulate ER-α36 to regulate the non-genomic signaling pathway through p-ERK1/2 rather than GPER [31]. GPER was also found to be necessary for the stimulated expression of ER-α36 which triggered by E2 [32]. Current knowledge suggests estrogen may activate GPER to induce ER-α36 expression (as shown in Figure 4).…”

Section: Introductionmentioning

confidence: 99%

The therapeutic target of estrogen receptor-alpha36 in estrogen-dependent tumors

Chen

López

et al. 2014

J Transl Med

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Estrogen receptor-alpha36 (ER-α36) is a new isoform of estrogen receptors without transcriptional activation domains of the classical ER-α(ER − α66). ER-α36 is mainly located in cytoplasm and plasma membrane. ER-α36 mediates non-genomic signaling and is involved in genomic signaling of other ERs. Recently ER-α36 is found to play a critical role in the development of estrogen-dependent cancers and endocrine resistance of breast cancer. The present article overviews and updates the biological nature and function of ER-α36, potential interaction of ER-α36 with other estrogen receptors and growth factor receptors, intracellular signaling pathways, potential mechanism by which ER-α36 may play an important role in the development of tumor resistance to endocrine therapies.

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Estrogens promote proliferation of the seminoma-like TCam-2 cell line through a GPER-dependent ERα36 induction

Cited by 31 publications

References 53 publications

Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells

Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells

Mammary epithelial cell phenotype disruption in vitro and in vivo through ERalpha36 overexpression

The therapeutic target of estrogen receptor-alpha36 in estrogen-dependent tumors

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