Preclinical Model of ER-positive breast cancer treated with thyroid hormone with or without tamoxifen
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ABSTRACT:
PROVIDER: PRJNA543104 | ENA |
REPOSITORIES: ENA
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Project description:Here, we treated a nove ER-positive PDX (UCD12) supplemented with estrogen (E2) with or without thyroid hormone (TH) and/or tamoxifen (Tam). Each treatment cohort (E2 alone, E2 + TH, E2 + Tam, E2+ TH+Tam) tumor growth over time was monitored. Tumors treated with TH continued to grow more that E2 alone. Tamoxifen blocked E2-mediated tumor growth, however in the presence of TH this was not seen. This analysis identified thyroid hormone as a potential driver of tumor progression in the context of estrogen receptor positive PDX tumor model.
2020-05-14 | GSE131276 | GEO
Project description:HOTAIR is up-regulated in tamoxifen-resistant breast cancer tissues compared to their primary counterparts. Mechanistically, HOTAIR is a direct target of ER-mediated transcriptional repression and is thus restored upon the blockade of ER signaling, either by hormone deprivation or tamoxifen treatment.
2015-10-01 | GSE71297 | GEO
Project description:HOTAIR is up-regulated in tamoxifen-resistant breast cancer tissues compared to their primary counterparts. Mechanistically, HOTAIR is a direct target of ER-mediated transcriptional repression and is thus restored upon the blockade of ER signaling, either by hormone deprivation or tamoxifen treatment.
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Project description:Thyroid hormone receptor beta is required for thyrotrpin regulation and thyroid hormone production.
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Project description:Using tadpoles mutant for thyroid hormone receptor alpha (thra), we show that TRa is required for thyroid hormone (T3) induction of cell proliferation in the brain. RNA-sequencing showed that the TRa is required for 95% of the gene regulation responses to T3.
2019-05-13 | GSE130816 | GEO
Project description:Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered an important site for thyroid action, the contribution of thyroid hormone receptor signaling, in muscle, to whole-body energy metabolism and body temperature has not been resolved. Here, we show that thyroid hormone-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRa1) in skeletal muscle, but that thyroid hormone induced elevation in body temperature is independent of muscle-TRa1. In slow-twitch soleus muscle, ablation of TRa1 leads to an altered fiber type composition toward a more oxidative phenotype, which, however, does not influence running capacity or motivation to voluntary running. RNA-sequencing of soleus muscle from WT mice and TRaHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, thus providing molecular clues pertaining to the mechanistic underpinnings of TRa1-linked control of whole-body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in thyroid hormone-stimulated increase in whole-body energy expenditure.
2020-09-21 | GSE146336 | GEO
Project description:Cerebellar post-natal development is particularly sensitive to thyroid hormone and low levels of thyroid hormone (hypothyroidism) result in permanent defects in cerebellar architecture and function. All cell types of the cerebellum are affected, but the main sign of hypothyroidism in mice is the persistence of the external granular layer, composed of mitotic neuronal precursors at P21. To make the genetic link between thyroid hormone and cerebellar development, we sought to identify new thyroid hormone target genes, in particular in granule cells which represent the vast majority of cerebellar cells.
2012-03-30 | GSE24793 | GEO
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:Cerebellar post-natal development is particularly sensitive to thyroid hormone and low levels of thyroid hormone (hypothyroidism) result in permanent defects in cerebellar architecture and function. All cell types of the cerebellum are affected, but the main sign of hypothyroidism in mice is the persistence of the external granular layer, composed of mitotic neuronal precursors at P21. To make the genetic link between thyroid hormone and cerebellar development, we sought to identify new thyroid hormone target genes, in particular in granule cells which represent the vast majority of cerebellar cells. Primary cultures of cerebellar neurons were made by dissociation of cerebella from newborn wild-type mice. These cells were plated 48 hours in serum-free medium to avoid invasion of the culture by glial cells. In order to include a kinetic and a maximum number of target genes, several cultures were either treated or left untreated as controls for 6 hours (T1), 16 hours (T2), 24 hours (T3) or 48 hours (T4) and results were pairwise compared for each time point.
2012-03-29 | E-GEOD-24793 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE16017: Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part B GSE16018: Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part C GSE16074: Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part A Refer to individual Series
2010-05-16 | E-GEOD-16075 | biostudies-arrayexpress