Similar Datasets
Project description:The function of USP36 in the ER positive Breast Cancer
| PRJNA1092965 | ENA
Project description:Preclinical model of obesity and ER-positive breast cancer
| PRJNA434156 | ENA
Project description:Primary ER-positive Breast Cancer Treated with Neoadjuvant Letrozole
| PRJNA272564 | ENA
Project description:This study is intended to investigate the differences in biological molecular expression upon HER2 status (HER2-positive and –negative) in AR-positive, ER-/PR-negative breast cancer. Results indicate that differentially expressed genes were involved in olfactory transduction, major histocompatibility complex, ECM-receptor interaction, focal adhesion, adherens junction, as well as protein processing in endoplasmic reticulum.
2019-06-30 | GSE92252 | GEO
Project description:Estrogen receptor (ER) signaling–dependent cancer cell growth is one of the major features of ER-positive breast cancer (BC). Inhibition of ER function is a standard and effective treatment for ER-positive tumors; however, ~20% of patients with ER-positive BC experience early or late recurrence. In this study, we examined intertumor heterogeneity from an epigenetic perspective based on the hypothesis that the intrinsic difference in epigenetic states around ER signaling pathway underlies endocrine therapy resistance. We profiled chromatin accessibility data from 42 BC samples, including 35 ER-positive human epidermal growth factor receptor 2 (HER2)-negative and 7 triple-negative tumors, identifying a subgroup of ER-positive BCs with a distinctive chromatin accessibility pattern including reduced accessibility to ER-responsive elements (EREs). The same subgroup was also observed in The Cancer Genome Atlas BC cohort. Despite the reduced accessibility to EREs, the expression of ER and potential ER target genes were not decreased in these tumors. Our findings highlight the existence of a subset of ER-positive BCs with unchanged ER expression but reduced EREs accessibility that cannot be distinguished by conventional immunostaining for ER. Future studies should determine whether these tumors are associated with resistance to endocrine therapy.
2023-01-09 | GSE222116 | GEO
Project description:The role of Hippo pathway in ER positive breast cancer
| PRJNA752105 | ENA
Project description:RanBP2 type and C3HC4 type zinc finger containing protein 1 (RBCK1,) is a 58 kDa protein containing N-terminal ubiquitin like (UBL) domain, npl4 type zinc finger (NZF) domain and catalytic carbon terminal RBR domain. It is known that it has abnormal expression in tumors, making it a valuable diagnostic marker and drug target. A large number of studies have confirmed that in ER positive breast cancer, about 25%-40% of the tumor showed a visible hypoxia area. Under hypoxia, tumor cells can activate HIF1 pathway and widely activate the expression of downstream genes. Hypoxia inducible factor HIF-1 is composed of HIF-1α and HIF-1β Two subunits, The protein level of HIF-1α is precisely regulated by oxygen concentration. Here, we report RBCK1, a RING family ubiquitin ligase that regulates HIF1α, promoting ER positive breast cancer growth and inhibiting apoptosis. Deletion of RBCK1 inhibits ER positive breast cancer growth and promotes cell death. RNA sequencing analysis showed that in ER positive breast cancer, RBCK1 may be an important modifier of HIF1α signal pathway. Further experiments showed that RBCK1 and HIF1α Interacts and inhibits HIF1α polyubiquitination to inhibit HIF1α degradation in ER positive breast cancer cells. These finding reveals a novel direct HIF1α regulator and a potential therapeutic target for ER positive breast cancer.
2022-02-12 | GSE196274 | GEO
Project description:Diagnostic samples from female breast cancer patients with ER-positive and HER2-normal tumors selected for neoadjuvant chemotehrapy.
2023-05-09 | GSE231629 | GEO
Project description:The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and drug resistance remain incompletely understood. Elevated expression of CCND1 is linked to enhanced invasiveness, poorer prognosis, and resistance to drug therapies in ER-positive breast cancer. In this study, we report that a highly expressed circular RNA (circRNA) derived from FOXK2, called circFOXK2, stabilizes CCND1 mRNA, thereby promoting cell cycle progression, cell growth, and endocrine therapy resistance in ER-positive breast cancer cells. Mechanistically, circFOXK2 binds directly to CCND1 mRNA via RNA-RNA pairing, recruiting the RNA-binding protein ELAVL1/HuR to stabilize CCND1 mRNA, thereby increasing CCND1 protein levels. Elevated CCND1 activates the CCND1-CDK4/6-p-RB-E2F signaling axis, driving the transcription of downstream E2F target genes and promoting the G1/S transition during cell cycle progression. Consequently, anti-sense oligonucleotide (ASO)-targeting circFOXK2 (ASO-circFOXK2) suppresses the growth of ER-positive breast cancer cells both in vitro and in vivo. Combination treatment with ASO-circFOXK2 and Tamoxifen shows synergistic effects. Moreover, ASO-circFOXK2 restores Tamoxifen sensitivity in Tamoxifen-resistant ER-positive breast cancer cells both in vitro and in vivo. The clinical relevance is underscored by the high expression of circFOXK2, which is positively correlated with that CCND1 expression in ER-positive breast cancer cell lines and clinical tumor tissues. Overall, our findings reveal the critical role of circFOXK2 in stabilizing the mRNA of the oncogene CCND1 and promoting cell cycle progression, identifying circFOXK2 as a potential therapeutic target for treating ER-positive breast cancer in clinical settings.
2024-12-25 | GSE284608 | GEO
Project description:Activating mutations of PIK3CA are the most frequent genomic alterations in estrogen receptor (ER)-positive breast tumors and selective PI3Kα inhibitors are in clinical development. The activity of these agents, however, is not homogenous and only a fraction of patients bearing PIK3CA-mutant ER-positive tumors benefit from single agent administration. Searching for mechanisms of resistance, we observed that suppression of PI3K signaling with different agents results in induction of ER-dependent transcriptional activity as demonstrated by changes in expression in genes containing ER binding sites, enhanced ER transcription and increased occupancy by the ER of promoter regions of upregulated genes. Furthermore, expression of ESR1 mRNA and ER protein levels themselves were also increased upon PI3K inhibition. These changes in gene expression were confirmed in vivo in xenograft and patient derived models and in tumors from patients undergoing treatment with the PI3Kα inhibitor BYL719. The observed effects on transcription were enhanced by the addition of estradiol and suppressed by the anti-ER therapies fulvestrant and tamoxifen. Fulvestrant markedly sensitized ER-positive tumors to PI3Kα inhibition. We propose that increased ER transcriptional activity may be a compensatory mechanism that limits the activity of PI3K inhibitors and that combined PI3K and ER inhibition is a rational approach to target these tumors. The aim of our study was to explore the mechanism by which combination of PI3K pathway inhibitors and estrogen receptor function blockade results in superior antitumor activity. We aimed to evaluate whether changes in ER function were influencing the clinical response to anti-PI3K therapy in ER-positive breast tumors that harbor PI3K pathway activation. For this purpose, we planned to use various specific PI3K inhibitors, namely: BYL719 (p110α specific catalytic inhibitor), GDC0941 (pan-PI3K inhibitor), GDC0032 and BAY80-6946 (p110sparing PI3K inhibitors) in a panel of ER-positive breast cancer cell lines and xenografts that harbor PIK3CA activating mutations. We also used MK2206 (pan-AKT allosteric inhibitor) to inhibit the PI3K pathway in ER-positive cell lines which activate this pathway through PTEN loss. Finally, in order to evaluate the role of ER up-regulation as a pro-survival signal in our in vitro and in vivo models, we planned to use the selective ER modulator 4-hydroxy-tamoxifen (4-OHT) and degrader fulvestrant. For the in vivo experiments, the number of animals in each group was calculated to measure a 25% difference between the means of placebo and treatment groups with a power of 80% and a p value of 0.01. Host mice carrying xenografts were randomly and equally assigned to either control or treatment groups. Animal experiments were conducted in a controlled and non-blinded manner. Moreover, we evaluated by means of RNAseq gene expression changes breast cancer patients that underwent BYL719 based therapy to validate our in vitro findings in terms of ER expression. In vitro experiments were performed at least two times and at least in triplicate for each replica.
2015-04-29 | E-GEOD-64033 | biostudies-arrayexpress