Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA377829 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Exome-sequencing of tamoxifen-resistant and -sensitive breast cancer cell lines.
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Project description:Tamoxifen-resistant human breast cancer cell lines
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Project description:MicroRNA expression profiling of tamoxifen sensitive and resistant ER+ breast cancer cell lines
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Project description:RNA-sequencing of tamoxifen-resistant and -sensitive breast cancer cell lines.
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Project description:Expression data from Tamoxifen resistant Breast Cancer Cell lines
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Project description:Tamoxifen, an antagonist to estrogen receptor (ER), is a first line drug used in breast cancer treatment. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying the resistance to tamoxifen, we established a tamoxifen-resistant cell line by treating the MCF7 breast cancer cell line with tamoxifen for over 6 months. We showed that this cell line exhibited resistance to tamoxifen both in vitro and in vivo. In order to quantify the phosphorylation alterations associated with tamoxifen resistance, we performed SILAC-based quantitative phosphoproteomic profiling on the resistant and vehicle-treated sensitive cell lines where we identified >5,600 unique phosphopeptides. We found phosphorylation levels of 1,529 peptides were increased (>2 fold) and 409 peptides were decreased (<0.5-fold) in tamoxifen resistant cells compared to tamoxifen sensitive cells. Gene set enrichment analysis revealed that focal adhesion pathway was the top enriched signaling pathway activated in tamoxifen resistant cells. We observed hyperphosphorylation of the focal adhesion kinases FAK1 and FAK2 in the tamoxifen resistant cells. Of note, FAK2 was not only hyperphosphorylated but also transcriptionally upregulated in tamoxifen resistant cells. Suppression of FAK2 by specific siRNA knockdown could sensitize the resistant cells to the treatment of tamoxifen. We further showed that inhibiting FAK activity using the small molecule inhibitor PF562271 repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 significantly associated with short metastasis-free survival of ER-positive breast cancer patients treated with tamoxifen-based hormone therapy. Our studies suggest that FAK2 is a great potential target for the development of therapy for the treatment of hormone refractory breast cancers.
2016-05-25 | PXD001812 | Pride
Project description:To gain new insight into the resistance to hormonal therapy in breast cancer, we generated a tamoxifen-resistant human breast cancer cell line T47D-TR by exposing estrogen-sensitive cell line T47D to increasing concentrations of 4-hydroxy tamoxifen (4-OHT) and identified its resistance with different ways. What we interested is the underlying mechanisms of breast cancer tamoxifen resistance which was not reported yet.Here, we detect the RNA sequence of both the two cell lines hoping to find some evidence.
2020-01-28 | GSE125738 | GEO
Project description:Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer. However, about 30% of such patients receiving tamoxifen as an adjuvant therapy experience recurrence within 15 years, and most patients with advanced disease eventually develop resistance to tamoxifen. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant human breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive MCF-7/S0.5 cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all TamRs using both sequencing and LNA-based quantitative PCR technologies. ER+ and tamoxifen sensitive breast cancer cell line (MCF-7/S0.5) and its derived tamoxifen resistant clones: TAMR-1, TAMR-4 and TAMR-8 were miRNA expression profiled in triplicates of each using Exiqon's miRCURY LNA based microRNA Ready-to-use PCR, Human panel I+II, V2.R (Exiqon, product number 203608).
2015-08-01 | E-GEOD-56411 | biostudies-arrayexpress
Project description:The goal of this experiment was to identify the putative mRNA targets of miR-29b-1 and miR-29a in LCC9 tamoxifen-resistant breast cancer cell lines relative to parental MCF-7 tamoxifen-sensitive cells
2017-08-11 | GSE81620 | GEO
Project description:Tamoxifen is an effective anti-estrogen treatment for patients with estrogen receptor-positive (ER+) breast cancer. However, about 30% of such patients receiving tamoxifen as an adjuvant therapy experience recurrence within 15 years, and most patients with advanced disease eventually develop resistance to tamoxifen. To elucidate the underlying molecular mechanisms of tamoxifen resistance, we performed a systematic analysis of miRNA-mediated gene regulation in three clinically-relevant tamoxifen-resistant human breast cancer cell lines (TamRs) compared to their parental tamoxifen-sensitive MCF-7/S0.5 cell line. Alterations in the expression of 131 miRNAs in tamoxifen-resistant vs. parental cell lines were identified, 22 of which were common to all TamRs using both sequencing and LNA-based quantitative PCR technologies.
2015-08-01 | GSE56411 | GEO