scholarly journals Estrogen receptor-α mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen

2005 ◽  
Vol 12 (4) ◽  
pp. 851-866 ◽  
Author(s):  
Amanda J M O’Donnell ◽  
Kenneth G Macleod ◽  
David J Burns ◽  
John F Smyth ◽  
Simon P Langdon
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Ovarian Carcinoma ◽  
Significant Role ◽  
Target Genes ◽  
De Novo ◽  
Estrogen Receptor Α ◽  
Ovarian Cancer Cells ◽  
Real Time Quantitative Pcr

Estrogens play a significant role in the development, growth, invasion and metastasis of ovarian tumors. The transcriptional program regulated by 17β-estradiol (E2) in human ovarian cancer cell lines was analyzed using cDNA microarrays containing 1200 cancer-related genes. Twenty-eight transcripts had at least a threefold change in expression in E2-treated PEO1 ovarian carcinoma cells compared with controls. These differences were confirmed by real-time quantitative PCR and shown to be dependent upon the expression of functional estrogen receptor-α (ERα). Consistent with this, these gene expression changes were blocked by the anti-estrogen tamoxifen. The use of ERα- and ERβ-specific ligands allowed molecular dissection of the E2 response and showed that ERα activation was responsible for the observed changes in gene expression, whereas ERβ played no significant role. Inhibition of de novo protein synthesis by cycloheximide was used to distinguish between primary and secondary target genes regulated by E2. Actinomycin D was used to show that changes in gene expression levels induced by E2 were a result of changes in transcription and not due to changes in mRNA stability. The results presented here demonstrate that estrogen-driven growth of epithelial ovarian carcinoma is mediated by activation of ERα-mediated, and not ERβ-mediated, transcription.

scholarly journals The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes

2021 ◽  
Vol 23 (1) ◽  
pp. 73
Author(s):  
Karolina Seborova ◽  
Alzbeta Kloudova-Spalenkova ◽  
Kamila Koucka ◽  
Petr Holy ◽  
Marie Ehrlichova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
De Novo ◽  
Ovarian Cancer Cells ◽  
In Vivo Models ◽  
Resistant Mouse

The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in ABCC3, CPS1, and TRIP6 gene expression in a breast cancer cell line resistant to paclitaxel. The present study aimed to investigate gene expression changes of these three candidate molecules in the highly resistant ovarian carcinoma cells in vitro and corresponding in vivo models treated with paclitaxel and new experimental Stony Brook taxanes of the third generation (SB-T-121605 and SB-T-121606). We also addressed their prognostic meaning in ovarian carcinoma patients treated with taxanes. We estimated and observed changes in mRNA and protein profiles of ABCC3, CPS1, and TRIP6 in resistant and sensitive ovarian cancer cells and after the treatment of resistant ovarian cancer models with paclitaxel and Stony Brook taxanes in vitro and in vivo. Combining Stony Brook taxanes with paclitaxel caused downregulation of CPS1 in the paclitaxel-resistant mouse xenograft tumor model in vivo. Moreover, CPS1 overexpression seems to play a role of a prognostic biomarker of epithelial ovarian carcinoma patients’ poor survival. ABCC3 was overexpressed in EOC tumors, but after the treatment with taxanes, its up-regulation disappeared. Based on our results, we can suggest ABCC3 and CPS1 for further investigations as potential therapeutic targets in human cancers.

scholarly journals Effect of estrogen receptor β agonists on proliferation and gene expression of ovarian cancer cells

BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Susanne Schüler-Toprak ◽  
Christoph Moehle ◽  
Maciej Skrzypczak ◽  
Olaf Ortmann ◽  
Oliver Treeck
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Estrogen Receptor Β ◽  
Ovarian Cancer Cells

Bile acids upregulate BRCA1 and downregulate estrogen receptor 1 gene expression in ovarian cancer cells

2018 ◽  
Vol 27 (6) ◽  
pp. 553-556 ◽  
Author(s):  
Qunyan Jin ◽  
Olivier Noel ◽  
Mai Nguyen ◽  
Lionel Sam ◽  
Glenn S. Gerhard
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Bile Acids ◽  
Ovarian Cancer Cells ◽  
Estrogen Receptor 1

scholarly journals The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Hidenori Machino ◽  
Syuzo Kaneko ◽  
Masaaki Komatsu ◽  
Noriko Ikawa ◽  
Ken Asada ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Metabolic Stress ◽  
Ovarian Cancer Cells ◽  
Hippo Signaling ◽  
High Grade ◽  
Gynecological Malignancy ◽  
Serous Ovarian Carcinoma

AbstractHigh-grade serous ovarian carcinoma (HGSOC) is the most aggressive gynecological malignancy, resulting in approximately 70% of ovarian cancer deaths. However, it is still unclear how genetic dysregulations and biological processes generate the malignant subtype of HGSOC. Here we show that expression levels of microtubule affinity-regulating kinase 3 (MARK3) are downregulated in HGSOC, and that its downregulation significantly correlates with poor prognosis in HGSOC patients. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells. The LKB1-MARK3 axis is activated by metabolic stress, which leads to the phosphorylation of CDC25B and CDC25C, followed by induction of G2/M phase arrest. RNA-seq and ATAC-seq analyses indicate that MARK3 attenuates cell cycle progression and angiogenesis partly through downregulation of AP-1 and Hippo signaling target genes. The synthetic lethal therapy using metabolic stress inducers may be a promising therapeutic choice to treat the LKB1-MARK3 axis-dysregulated HGSOCs.

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

2009 ◽  
Vol 202 (1) ◽  
pp. 167-177 ◽  
Author(s):  
Liyuan Tian ◽  
Zhiqiang Wu ◽  
Yali Zhao ◽  
Yuanguang Meng ◽  
Yiling Si ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Estrogen Receptor Α ◽  
Ovarian Cancer Cells ◽  
Induction Effect ◽  
Skov3 Cell ◽  
Signaling Transduction ◽  
Estrogen Response ◽  
Skov3 Cells

Previously, we investigated the induction effect of LRP16 expression by estrogen (17β-estradiol, E2) and established a feed-forward mechanism that activated estrogen receptor α (ERα) transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ERα signaling transduction by functioning as an ERα coactivator. In this study, we demonstrated that LRP16 expression was upregulated in E2-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 ERα 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 ERα at LRP16 promoter in the absence of estrogen; however, ERα was largely released from the DNA upon E2 stimulation. Modulation in LRP16 expression level did not significantly change the proliferation rate of SKOV3 cells and the growth responsiveness of cells to E2. Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated estrogen response element-dependent ERα reporter gene activity and E2-induced c-Myc expression. Our study suggests a novel mechanism of estrogen resistance of ovarian cancer by which estrogen-repressed signaling pathway antagonizes estrogen-activated signaling transduction.

scholarly journals Activation of estrogen receptor α by estradiol and cisplatin induces platinum-resistance in ovarian cancer cells

2016 ◽  
Vol 18 (9) ◽  
pp. 730-739 ◽  
Author(s):  
Sohei Matsumura ◽  
Tsuyoshi Ohta ◽  
Keiko Yamanouchi ◽  
Zhiyang Liu ◽  
Takeshi Sudo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Estrogen Receptor Α ◽  
Ovarian Cancer Cells ◽  
Platinum Resistance
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