Molecular profiling of aromatase inhibitor-treated post-menopausal breast tumors identifies immunerelated correlates of resistance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA642790 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Molecular profiling of 16 week aromatase inhibitor-treated post-menopausal breast tumors
| PRJNA679589 | ENA
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: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: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:Gene expression profiling was carried out on peripheral blood mononuclear cells from 45 adult females. The primary research question is whether leukocyte gene expression differs in individuals with varying levels of estrogen signaling. Experiment Overall Design: Study includes adult females, 11 of whom were pre-menopausal, 12 of whom were post-menopausal, 10 of whom were post-menopausal and receiving aromatase inhibitors, and 12 of whom were receiving tamoxifen.
2009-08-15 | E-GEOD-12517 | biostudies-arrayexpress
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:Background: Breast cancer patients present lower 1,25(OH)2D3 or 25(OH)D3 serum levels than unaffected women. Although 1,25(OH)2D3 pharmacological concentrations of 1,25(OH)2D3 may exert antiproliferative effects in breast cancer cell lines, much uncertainty remains about the effects of calcitriol supplementation in tumor specimens in vivo. We have evaluated tumor dimension (ultrassonography), proliferative index (Ki67 expression), 25(OH)D3 serum concentration and gene expression profile, before and after a short term calcitriol supplementation (dose to prevent osteoporosis) to post-menopausal patients. Results: Thirty three patients with operable disease had tumor samples evaluated. Most of them (87.5%) presented 25(OH)D3 insufficiency (<30 ng/mL). Median period of calcitriol supplementation was 30 days. Although tumor dimension did not vary, Ki67 immunoexpression decreased after supplementation. Transcriptional analysis of 15 matched pre/post-supplementation samples using U133 Plus 2.0 GeneChip (Affymetrix) revealed 18 genes over-expressed in post-supplementation tumors. As a technical validation procedure, expression of four genes was also determined by RT-qPCR and a direct correlation was observed between both methods (microarray vs PCR). To further explore the effects of near physiological concentrations of calcitriol on breast cancer samples, an ex vivo model of fresh tumor slices was utilized. Tumor samples from another 12 post-menopausal patients were sliced and treated in vitro with slightly high concentrations of calcitriol (0.5nM), that can be attained in vivo, for 24 hours In this model, expression of PBEF1, EGR1, ATF3, FOS and RGS1 was not induced after a short exposure to calcitriol. Conclusions: In our work, most post-menopausal breast cancer patients presented at least 25(OH)D3 insufficiency. In these patients, a short period of calcitriol supplementation may prevent tumor growth and reduce Ki67 expression, probably associated with discrete transcriptional changes. This observation deserves further investigation to better clarify calcitriol effects in tumor behavior under physiological conditions.
2012-02-18 | GSE35925 | GEO
Project description:The human endometrium is a highly regenerative tissue that undergoes cyclical proliferation, differentiation and shedding each month. The upper functionalis layer of the endometrium is shed in response to circulating levels of estrogen and progesterone, while the lower basalis layer remains. Clonogenic epithelial stem/progenitor cells likely responsible for regenerating endometrial epithelium have been identified in pre-menopausal (Pre-M) and post-menopausal (Post-M) endometrium and may reside in the basalis layer. We undertook a transcriptional profiling of purified epithelial cells from full-thickness Pre-M and Post-M endometrium to identify differentially expressed genes. The hypothesis tested in the present study was that Post-M endometrial epithelial gene profile would be similar to the quiescent basalis epithelium of Pre-M endometrium. We found striking differential gene expression of many Wnt family members between Pre-M and Post-M and other stem cell network genes. Comparative analysis of our endometrial epithelial gene expression profiles to that of endometrial epithelial cells in remodelling endometrium also provides new evidence showing that Post-M endometrial epithelium has a similar gene signature to that of basalis epithelium of menstrual endometrium. Human endometrial tissue was obtained from 8 pre-menopausal and 3 post-menopausal women undergoing hysterectomy for various benign gynaecologic conditions. Endometrial tissue was digested and isolated using combination of DNase and collagenase. Anti-human EpCAM antibody-coated magnetic Dynabeads was used to positively select total epithelial cells from the digested single cell suspensions. Total RNA was extracted from the purified endometrial epithelial cells and hybridised to Illumina Sentrix HT12 beadchip. Resulting data was compared between pre-menopausal and post-menopausal samples.
2012-04-10 | E-GEOD-35221 | biostudies-arrayexpress