Molecular profiling of 16 week aromatase inhibitor-treated post-menopausal breast tumors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA679589 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To identify the effect of 16 weeks of neoadjuvant anastrozole treatment on gene expression profiles of oestrogen receptor positive breast tumours from post-menopausal patients.
2021-04-01 | GSE161830 | GEO
Project description:To identify in clinical breast cancer those genes and pathways most associated with resistance to aromatase inhibitors by examining the global transcriptional effects of aromatase inhibitor (AI) treatment. Analysis of gene-expression measured in core-cut biopsies at baseline and surgery from patients received 2-week’s presurgical AI revealed: i) the molecular response to AI treatment varies greatly between patients, consistent with the variable clinical benefit from AI treatment; ii) higher baseline expression of an inflammatory signature is associated with poor antiproliferative response, and should be assessed further as a novel biomarker and potential target for AI-treated patients.
2020-06-29 | GSE153470 | GEO
Project description:Molecular profiling of aromatase inhibitor-treated post-menopausal breast tumors identifies immunerelated correlates of resistance
| PRJNA642790 | ENA
Project description:Aromatase contributes to the maintenance of bone mass because male patients with loss-of-function mutations of CYP19A1 exhibit bone loss. Furthermore, treatment with aromatase inhibitor also causes bone loss in men as well as post-menopausal women, in whom serum estrogen level is very low, suggesting that a part of the anabolic effects of testosterone in men is dependent on estradiol (E2) biosynthesized by aromatase in non-gonadal tissues. However, it remains unclear how locally biosynthesized E2 contributes to the maintenance of bone mass. We examined the function of aromatase in local tissues rather than gonad using cell type specific aromatase KO mice. Because osteoblast-specific aromatase KO mice exhibited no bone phenotype, we focused on adipose tissue, which is known as reservoir of steroid hormones, and analyzed the bone phenotypes of adipose tissue-specific aromatase KO mice (AroΔaP2). Sixteen-week-old male AroΔaP2 mice exhibit significantly lower bone mineral density in tibia and femur, especially in trabecular bone compared to the control. Bone histomorphometry showed that AroΔaP2 mice exhibited an osteomalacia-like bone phenotype with increased osteoid volume and width, and decreased osteoclast area and numbers. Moreover, serum PI and renal phosphorus reabsorption were significantly decreased but FGF23 level was decreased in AroΔaP2, suggesting that an osteomalacia-like phenotype in AroΔaP2 was not caused by abnormal FGF23 level. Finally, we analyzed NaPi2a and NaPi2c, a phosphate transporter localized in the kidney, and found that protein levels in renal brush border membrane vesicles were decreased in AroΔaP2. These results indicate that locally biosynthesized estrogens by aromatase in adipocytes can play a significant role in bone mass maintenance via regulate phosphorus reabsorption in kidney by NaPi2.
2024-07-22 | GSE263849 | GEO
Project description:To identify the genes which have relation to aromatase-inhibitor-resistance, we compared the gene expression of aromatase-inhibitor-resistant cell, A3, with that of parent cell line, T-47D.
2014-04-01 | GSE51390 | GEO
Project description:To identify the genes which have relation to aromatase-inhibitor-resistance, we compared the gene expression of aromatase-inhibitor-resistant cell, A3, with that of parent cell line, T-47D. Because A3 showed remarkable cell proliferation by 1nM Dihydrotestosterone(DHT), cells were cultured with DHTand bicalutamide for 24h, and total RNA was extracted.
2014-04-01 | E-GEOD-51390 | biostudies-arrayexpress
Project description:Osteoporosis is a multifactorial disease with genetic and strong epigenetic component. In spite of enormous candidate gene association studies, the etiology and molecular mechanism of disease is not fully known. This study is undertaken to identify new markers of osteoporosis which could be vital in diagnosis and prognosis of disease, genome-wide microarray expression approach was employed on post menopausal Indian females living in same geographical area with almost similar life-style. To validate microarray gene expression pattern, qRT-PCR was performed on top 5 genes on osteoporotic (n =32) and non-osteoporotic (n=15) post menopausal females
2017-06-29 | GSE100609 | GEO
Project description:Understanding the complex molecular mechanisms underlying resistance to endocrine therapy is a major challenge in the treatment of estrogen receptor-positive (ER+) breast cancers. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) signaling via the receptor tyrosine kinase RET promotes estrogen independent activation of ER. Here we have addressed the relevance of GDNF-RET signaling in response to aromatase inhibitor treatment and explored the efficacy of using RET inhibitors in breast cancer models of aromatase inhibitor response and resistance. A GDNF-response gene set, identified from gene expression profiling, was demonstrated to be an independent prognostic marker of poor patient outcome and, importantly, to be predictive of poor response to aromatase inhibitor treatment and development of resistance. The relevance of these findings was validated first by demonstrating an association of RET protein expression in an independent cohort of aromatase inhibitor resistant patient samples. Second, in in vitro models, GDNF-mediated RET signaling was demonstrated to enhance the survival of aromatase inhibitor resistant cells and to increase resistance in aromatase inhibitor sensitive cells. These effects could be reversed by targeting GDNF/RET signaling with the RET selective inhibitor NVP-BBT594 thus identifying GDNF-RET signaling as a potential therapeutic target, particularly in breast cancers resistant to aromatase inhibitors.<br>MCF7 cells were E2-deprived by culturing in phenol red-free RPMI 1640 supplemented with 10% DCC for 3 days and then serum-starved overnight in the presence or absence of fulvestrant (ICI182,780) (100 nM). The following day, cells were treated with GDNF (20 ng/ml) for 0, 4, 8, 24 and 48 hours in the presence or absence of fulvestrant (ICI182,780) (100 nM).
2013-01-17 | E-MEXP-3662 | biostudies-arrayexpress
Project description:Fresh-frozen primary cancer specimens of 107 breast cancer patients whose metastases were treated with first-line aromatase inhibitors were evaluated for their whole genome mRNA expression profiles.
2013-12-05 | GSE41994 | GEO
Project description:To explore the transcriptional effects of aromatase inhibitors on sex differentiation of zebrafish, we exposed 3-month-old zebrafish (AB strain) to the third generation aromatase inhibitor Exemestane (CAS: 107868-30-4) and characterized transcript abundance among testes and ovaries after 32 days of drug exposure. After the drug treatment, we dissected zebrafish gonads, isolated polyA+ RNA and performed high-throughput RNA-Seq analysis.
2019-12-07 | GSE123439 | GEO