Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA124445 | ENA |
REPOSITORIES: ENA
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Project description:Background: Aldo-keto reductase (AKR) 1C family member 3 (AKR1C3), one of four identified human AKR enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa) aggressiveness. Here we provide initial evidence for potential roles of AKR1C3 in PCa progression. Methods: Spatial distribution of AKR1C3 was analyzed using immunohistochemical staining in prostate adenocarcinoma tissue array. Human PCa PC-3 cells were stably transfected with AKR1C3 cDNA to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analyses were performed to identify pathways that are activated by elevated AKR1C3 expression in PCa cells. Functional confirmation of microarray and bioinformatics results was performed by immunoblot analysis and an in vitro Matrigel angiogenesis assay. Results: Elevated AKR1C3 expression was specifically limited to human prostate adenocarcinoma. Microarray and bioinformatics analysis suggested that elevated AKR1C3 expression in PC-3 cells modulates estradiol and androgen metabolism and activates insulin growth factor (IGF)-1 and Akt signaling pathways. Immunoblots confirmed that phosphorylated levels of IGF-1 receptor (IGF-1R) and Akt are significantly up-regulated in PC3-AKR1C3 as compared to mock transfectants. PC3-AKR1C3 transfectants promoted endothelial cell tube formation in Matrigel as compared to parental PC-3 cells and mock transfectants. Conclusion: Microarray and bioinformatics data followed by biological analyses suggest that elevated AKR1C3 expression in PC-3 cells promotes PCa angiogenesis and aggressiveness. These results suggest AKR1C3 can promote the aggressiveness of PCa through modulating estrogen and androgen metabolism with subsequent activation of growth factor IGF-1 and cytoplasmic Akt signaling pathways. Total RNA from mock- and ACR1C3 transfected PC-3 cells was isolated, with 2 or 3 biological replicates each. Gene expression data from AKR1C3 transfected PC-3 cells were compared with mock-transfected data.
2010-08-10 | E-GEOD-20956 | biostudies-arrayexpress
Project description:Background: Aldo-keto reductase (AKR) 1C family member 3 (AKR1C3), one of four identified human AKR enzymes, catalyzes steroid, prostaglandin, and xenobiotic metabolism. In the prostate, AKR1C3 is up-regulated in localized and advanced prostate adenocarcinoma, and is associated with prostate cancer (PCa) aggressiveness. Here we provide initial evidence for potential roles of AKR1C3 in PCa progression. Methods: Spatial distribution of AKR1C3 was analyzed using immunohistochemical staining in prostate adenocarcinoma tissue array. Human PCa PC-3 cells were stably transfected with AKR1C3 cDNA to establish PC3-AKR1C3 transfectants. Microarray and bioinformatics analyses were performed to identify pathways that are activated by elevated AKR1C3 expression in PCa cells. Functional confirmation of microarray and bioinformatics results was performed by immunoblot analysis and an in vitro Matrigel angiogenesis assay. Results: Elevated AKR1C3 expression was specifically limited to human prostate adenocarcinoma. Microarray and bioinformatics analysis suggested that elevated AKR1C3 expression in PC-3 cells modulates estradiol and androgen metabolism and activates insulin growth factor (IGF)-1 and Akt signaling pathways. Immunoblots confirmed that phosphorylated levels of IGF-1 receptor (IGF-1R) and Akt are significantly up-regulated in PC3-AKR1C3 as compared to mock transfectants. PC3-AKR1C3 transfectants promoted endothelial cell tube formation in Matrigel as compared to parental PC-3 cells and mock transfectants. Conclusion: Microarray and bioinformatics data followed by biological analyses suggest that elevated AKR1C3 expression in PC-3 cells promotes PCa angiogenesis and aggressiveness. These results suggest AKR1C3 can promote the aggressiveness of PCa through modulating estrogen and androgen metabolism with subsequent activation of growth factor IGF-1 and cytoplasmic Akt signaling pathways.
2010-08-10 | GSE20956 | GEO
Project description:Expression data from docetaxel-resistant prostate cancer cell lines
2025-01-24 | E-GEOD-33455 | ExpressionAtlas
Project description:Molecular Response of Chorioretinal Endothelial Cells to Complement Injury: Implications for Macular Degeneration
2023-06-15 | E-GEOD-70806 | ExpressionAtlas
Project description:Alpha-parvin (PARVA) is known to involve in the linkage of integrins, regulation of actin cytoskeleton dynamics, and cell survival. However, the role of PARVA in cancer progress is still unclear. Here, we identify PARVA as a potential oncogene from a lung cancer invasion cell line model by expression microarrays. Overexpression of PARVA enhances cell invasion, colony formation ability, and endothelial cell tube formation but knockdown of PARVA inhibits invasion and tube formation in vitro. PARVA also promotes tumorigenicity, angiogenesis, metastasis and mortality by in vivo tumorigenesis and metastasis mouse models. To explore the underlying mechanism, the PARVA-regulated signaling pathways were analyzed in PARVA-overexpressing cells compare with mock controls by expression microarrays. We used microarrays to profile the global gene expression of PARVA-overexpressing cells compared with mock control cells and identified the pathways involved in PARVA-induced biofunctional alterations.
2016-08-25 | GSE50657 | GEO
Project description:Transcription profiling by high throughput sequencing in castration resistant prostate cancer cell lines
2025-01-24 | E-GEOD-58966 | ExpressionAtlas
Project description:The development of resistance to current standard-of-care treatments, such as androgen receptor (AR) targeting therapies, remains a major challenge in the management of advanced prostate cancer. There is an urgent need for new therapeutic strategies targeting key resistant drivers such as AR variants like AR-V7 and steroidogenic enzymes such as AKR1C3 to overcome drug resistance and improve outcomes for patients with advanced prostate cancer. Here we have designed, synthesized, and characterized a novel class of LX compounds targeting both the AR/AR-Variants and AKR1C3 pathways. Molecular docking and in vitro studies demonstrated that LX compounds bind to the AKR1C3 active sites and inhibit AKR1C3 enzymatic activity. LX compounds were also shown to reduce AR/AR-V7 expression and inhibit their target gene signaling. LX1 inhibited the conversion of androstenedione into testosterone in tumor-based ex vivo enzyme assays. In addition, LX1 inhibited the growth of cells resistant to antiandrogens including enzalutamide, abiraterone, apalutamide and darolutamide in vitro. A synergistic effect was observed when LX1 was combined with antiandrogens and taxanes, indicating the potential for this combination in treating resistant prostate cancer. Treatment with LX1 significantly decreased tumor volume, serum PSA levels, as well as reduced intratumoral testosterone levels, without affecting mouse body weight. Furthermore, LX1 was found to overcome resistance to enzalutamide treatment, and its combination with enzalutamide further suppressed tumor growth in both the CWR22Rv1 xenograft and LuCaP35CR PDX models. Collectively, the dual effect of LX1 in reducing AR signaling and intratumoral testosterone, along with its synergy with standard therapies in resistant models, underscores its potential as a valuable treatment option for advanced prostate cancer.
2024-07-18 | GSE271696 | GEO
Project description:Our preliminary studies performed in vitro show that MDA-MB-231-FOXC1 cell, which were used to mimic the lung-colonizing triple-negative breast cancer cells, was an indispensable component for the induction of migration and tube formation of lung endothelial cells. Moreover, our results further show that mouse lung fibroblast-derived chemokines CCL2/7 act on MDA-MB-231-FOXC1 cells, which mediates the migration and tube formation of lung endothelial cells in vitro. To understand the signaling pathways activated by CCL2/7 in MDA-MB-231-FOXC1 cells, we performed RNA-Seq assay.
2019-05-18 | GSE131383 | GEO
Project description:Prostate-specific membrane antigen (PSMA) protein expression is induced during prostate cancer progression and metastasis. Recently, we reported that PSMA-positive vesicles released by prostate cancer cell lines enhanced vascular endo-thelial cell angiogenesis and that PSMA may be involved in tumor angiogenesis. Simi-larly, it is known that PSMA is upregulated in peritumoral vessels in renal cell carcinoma (RCC). In this study, we investigated the significance and molecular function of PSMA in RCC. PSMA immunohistochemical staining confirmed PSMA presence only in peri-nephric tumor vessels, and PSMA intensity was strongly correlated with recurrence rate and venous invasion. Spatial gene expression analysis revealed that FOLH1 expression, which codes PSMA, was upregulated in tumor blood vessels around renal cancer, and that angiogenesis-related pathways were enhanced. The 10,000 g pellet fraction of the renal cancer cell lines Caki1- and ACHN-conditioned medium (CM) in-duced PSMA positivity in human umbilical vein endothelial cells (HUVECs) and en-hanced tube formation. Mass spectrometry indicated that the 10,000 g pellet fraction contained various kinds of growth factors, like GDF15 and MYDGF. RNA sequencing showed that supplementing HUVECs with RCC cell CM-enhanced angiogenesis-related signaling pathways. Conclusively, microvesicle components secreted by RCC cells transform vascular endothelial cells into PSMA-positive cells, enhancing angiogenesis.
2025-03-23 | GSE289717 | GEO
Project description:The androgen receptor (AR) mediates the action of androgens by binding to androgen-responsive elements (AREs) and subsequently regulating target genes involved in prostate carcinogenesis. The precise locations, true nature, and functional roles of AREs in human prostate cancer are still unknown. Here we redefine AREs by motif-resolution AR chromatin immunoprecipitation-exonuclease (ChIP-exo) assay in human prostate cancer cells and tumors. Surprisingly, we find that, in addition to canonical full-length AREs and half-site-like AREs, a significant portion of the four redefined ARE categories comprises non-canonical full-length AREs. The redefined AREs in enhanced AR binding regions in prostate tumors versus paired non-malignant adjacent tissues regulate a prostate cancer-relevant gene network not only centered on AR, but more interestingly, on novel AR target genes mTOR, BIRC5 and BCL2L1 involved in prostate cancer cell growth and survival. The precise redefinition of AREs has important implications for understanding how AR contributes to prostate carcinogenesis. FOXA1 ChIP-exo
2015-01-01 | E-GEOD-43678 | biostudies-arrayexpress