Protein Kinase C<i>α</i>Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells

Thorne, Alicia; Jackson, Twila A.; Willis, Van C; Bradford, Andrew P.

doi:10.1155/2013/537479

Cited by 8 publications

(5 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most endometrial adenocarcinomas are characterized by positive nuclear estrogen receptor (ER) expression and responsiveness to hormone stimulation. Increasing evidence indicates that prolonged estrogen exposure is associated with initiation of type 1 endometrioid cancers (29)(30)(31). Estrogen exposure was found to result in an overall physiological response within several hours by a genomic mechanism which depends on estrogen binding to nuclear ER resulting in mRNA transcription and protein synthesis of target genes.…”

Section: Discussionmentioning

confidence: 99%

Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway

et al. 2016

View full text Add to dashboard Cite

Extensive exposure to estrogen is generally acknowledged as a risk factor for endometrial cancer. Given that the accumulation of adipocytes also contributes to the increased production of estrogen, in the present study, we evaluated the expression of the fat mass and obesity-associated (FTO) gene in endometrial tumor tissues and further explored the mechanism of how estrogen facilitates FTO nuclear localization and promotes endometrial cancer cell proliferation. Immunohistochemical (IHC) staining assay was used to detect the FTO expression in endometrial tumor samples. Western blotting was performed to investigate the mechanism of estrogen-induced FTO nuclear localization. siRNA was used to knock down ERα and further explore its role in FTO nuclear localization. MTT assay was carried out to determine cell proliferation. We found that FTO was overexpressed in endometrial carcinoma tissues and served as a poor prognostic marker. Additionally, estrogen induced FTO nuclear accumulation via the mTOR signaling pathway and the nuclear localization was ERα-dependent, which contributed to enhanced proliferative activity. Therefore, the present study provides new insight into the mechanisms of estrogen-induced proliferation, implying the possibility of using FTO as a potential therapeutic target for the treatment of endometrial cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Although these upstream regulators of ERα mainly promote the proliferation of EC, they have also been shown to have some effects on migration (70,71). In addition, protein kinase C α (PKCα) expression stimulates the ligand-independent activation of ER-dependent promoters to enhance the transcriptional capacity of ERα, thereby inducing endometrial proliferation (72). Furthermore, Frigo et al (73) showed that p38 promotes the proliferation of EC cells by stimulating ERα-mediated transcription via phosphorylation of the co-activator glucocorticoid receptor-interacting protein 1.…”

Section: Roles Of Erα In Ecmentioning

confidence: 99%

Roles of estrogen receptor α in endometrial carcinoma (Review)

Ge,

Ni,

et al. 2023

Oncol Lett

View full text Add to dashboard Cite

Endometrial carcinoma (EC) is a group of endometrial epithelial malignancies, most of which are adenocarcinomas and occur in perimenopausal and postmenopausal women. It is one of the most common carcinomas of the female reproductive system. It has been shown that the occurrence and development of EC is closely associated with the interaction between estrogen (estradiol, E2) and estrogen receptors (ERs), particularly ERα. As a key nuclear transcription factor, ERα is a carcinogenic factor in EC. Its interactions with upstream and downstream effectors and co-regulators have important implications for the proliferation, metastasis, invasion and inhibition of apoptosis of EC. In the present review, the structure of ERα and the regulation of ERα in multiple dimensions are described. In addition, the classical E2/ERα signaling pathway and the crosstalk between ERα and other EC regulators are elucidated, as well as the therapeutic targeting of ERα, which may provide a new direction for clinical applications of ERα in the future. Contents1. Introduction 2. Structure of ERα 3. Regulation of ERα 4. Classical E2/ERα signaling pathway 5. Roles of ERα in EC 6. Clinical application 7. Discussion

show abstract

“…At present, studies have shown that estrogen is involved in the activation of PKC signaling pathway and is an important starting valve for PKC activation [15][16][17]. Does PKC participate in the regulation of estrogen on intestinal glucose absorption?…”

Section: Effect Of Pkc Pathway On Estrogen-mediated Glucose Absorptio...mentioning

confidence: 99%

Estrogen regulates duodenal glucose absorption through the effect of estrogen receptor-α on glucose transporters

Shan

Ding

Xie

et al. 2022

Preprint

View full text Add to dashboard Cite

Estrogen deficiency is an important reason for the obesity of menopause, but the specific mechanism is unclear. Here, we investigated the effect of estrogen on glucose absorption. The experiments were performed in human, mice and SCBN cells. We first observed the correlation between estrogen and blood glucose in women, which found that blood glucose was significantly higher in the premenstrual phase than in the preovulatory phase of young women. Similarly, with serum estradiol level decreased in ovariectomized (OVX) mice, ER-α and ER-β in the duodenum reduced, the weight, abdominal fat and blood glucose increased significantly. However, interestingly, the expression of SGLT1 and GLUT2 and the glucose absorption in duodenal decreased significantly. It was further confirmed that estrogen could significantly up-regulate the expression of SGLT1 and GLUT2 in SCBN cells, and this trend can be reversed after silencing ER-α, but it doesn’t work after silencing ER-β, suggesting ER-α may be the key receptor of estrogen regulating glucose transporter. Mechanism study found that estrogen downstream can activate PKC pathway. Overall, our findings indicate that estrogen promotes glucose absorption, estrogen and its receptor (ER-α) deficiency can inhibit the expression of SGLT1 and GLUT2 through PKC signaling pathway, thereby reducing the glucose absorption.

show abstract

Protein Kinase CαModulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells

Cited by 8 publications

References 54 publications

Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway

Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway

Roles of estrogen receptor α in endometrial carcinoma (Review)

Estrogen regulates duodenal glucose absorption through the effect of estrogen receptor-α on glucose transporters

Contact Info

Product

Resources

About