Opposing effects of estrogen and Runx2 on breast cancer cell proliferation: identification of a reciprocally-regulated gene signature with clinical prognostic value.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30597 | GEO | 2012/03/06
SECONDARY ACCESSION(S): PRJNA144569
REPOSITORIES: GEO
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Project description:Analysis of reciprocal modulation of Runx2 and E2 signaling in BCA. Our objective was to investigate whether the interaction between estrogen and Runx2 signaling in breast cancer (BCa) could help refine an estrogen-responsive gene signature with improved prognostic value. MCF7/Rx2dox BCa cells conditionally expressing Runx2 upon doxycycline treatment were treated with estradiol and/or doxycycline to induce Runx2, and global gene expression was profiled to define genes regulated by estradiol, Runx2, or both.
2012-03-06 | E-GEOD-30597 | biostudies-arrayexpress
Project description: Not available
| S-ECPF-GEOD-30597 | biostudies-other
Project description:Primary osteoblast NEMCO cells have been transduced with lentivirus conditionally (doxycycline) expressing RUNX2 and treated with E2 to demonstrate effects of estrogen signaling on RUNX2 response
2016-02-01 | GSE65745 | GEO
Project description:Primary osteoblast NEMCO cells have been transduced with lentivirus conditionally (doxycycline) expressing RUNX2 and treated with E2 to demonstrate effects of estrogen signaling on RUNX2 response NEMCO cells kept at charcoal stripped serum have been treated with dox and/or E2 for 48h
2016-02-01 | E-GEOD-65745 | biostudies-arrayexpress
Project description:We performed ChIP-seq on MCF7 cells in an effort to discern differential binding patterns between wild type MCF7s and MCF7s that have acquired resistance to Tamoxifen and Estrogen deprivation. Furthermore, we also performed an HAtag ChIP on a DOX inducible RUNX2 overexpression MCF7 cell line. We also performed RNA-seq on MCF7 cells to determine transciptional changes after acquisition of Tamoxifen resistance, and also transciptional changes in a DOX inducible RUNX2 overexpression model.
2017-03-01 | GSE86538 | GEO
Project description:Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/- mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/- mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/- mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/- and double mutant Axin2-/-:Runx2+/- mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/- mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/- mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. 4 mice per genotype X 4 genotypes: wildtype (WT), Runx2+/- (R-Het), Axin2-/- (A-KO), Axin2-/-:Runx2+/- (A-KO:R-Het). Total = 16 samples
2014-07-04 | E-GEOD-59079 | biostudies-arrayexpress
Project description:Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/-M-BM- mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/-M-BM- mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/-M-BM- mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/-M-BM- and double mutant Axin2-/-:Runx2+/-M-BM- mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/-M-BM- mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/-M-BM- mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. 4 mice per genotype X 4 genotypes: wildtype (WT), Runx2+/- (R-Het), Axin2-/- (A-KO), Axin2-/-:Runx2+/- (A-KO:R-Het). Total = 16 samples
2014-07-04 | E-GEOD-59081 | biostudies-arrayexpress
Project description:Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/- mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/- mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/- mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/- and double mutant Axin2-/-:Runx2+/- mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/- mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/- mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation.
2014-07-04 | GSE59081 | GEO
Project description:Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/- mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/- mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/- mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/- and double mutant Axin2-/-:Runx2+/- mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/- mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/- mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation.
2014-07-04 | GSE59079 | GEO
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with a high incidence of relapse. Here we show that Runt-related transcription factor 2, RUNX2 is upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or immature phenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, while it reciprocally binds the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 is required for survival in immature and KMT2A-R T-ALL in vitro and in vivo. We report a direct transcriptional regulation of CXCR4 signaling by RUNX2, which thereby promotes cell migration and adhesion. Functionally, RUNX2 impacts T-ALL cell homing and exacerbates T-ALL progression to medullary and extramedullary sites. We demonstrate that RUNX2 enables these energy-demanding processes by increasing metabolic activity in T-ALL cells through positive regulation of both glycolysis and oxidative phosphorylation. Concurrently, RUNX2 upregulation results in increased mitochondrial dynamics and biogenesis in T-ALL cells. As a proof of concept, immature and KMT2A-R T-ALL cells are vulnerable to pharmacological targeting of the interaction of RUNX2 with its co-factor CBFβ. In conclusion, we identify RUNX2 a dependency factor in immature and KMT2A-R T-ALL that regulates cell metabolism and disease progression
2020-06-05 | GSE151819 | GEO