25D3 and 1,25D3 target gene profiles in LNCaP
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PROVIDER: PRJNA420078 | ENA |
REPOSITORIES: ENA
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Project description:Most prostate cancers depend on androgen and androgen receptor signaling for their proliferation and development, which underpins the efficacy of antiandrogens as powerful therapeutic agents for prostate cancers. On the other hand, interaction between AR and other nuclear hormone receptors (NRs) such as glucocorticoid receptor in the prostatic cancer or between AR and ER in breast cancers depicts the close association or “crosstalk” of AR with other NRs in terms of the new approach toward the management of hormone-resistant prostate/breast cancers. Along with this line, chemopreventive and antiproliferative action of 1,25(OH)2D3 (abbreviated as 1,25D3), an active metabolite of vitamin D3, during the management of prostate and/or breast cancers has been recently rigorously argued. We found that in its physiological concentration, 25(OH)D3 (abbreviated as 25D3), the precursor metabolite of 1,25D3 and widely-recognized as an inactive vitamin D because of its much weaker binding activity to vitamin D receptor (VDR) compared to 1,25D3, has a gene transcription profile similar to 1,25D3 in some prostate cancers. In this study, we investigated whole genome target gene profiles and intracellular behaviors of VDR after administration of 25D3 or 1,25D3 in prostate cancer LNCaP cells to elucidate the hormonal activity of 25D3. First, we confirmed that LNCaP cells possessed functional 25D3-VDR as well as 1,25D3-VDR signaling systems by qRT-PCR. By immunofluorescent examination of nuclear translocation, western blotting and most importantly, knockdown of CYP27B1 and/or VDR after the introduction of the respective siRNA into these cells, we found that, just like 1,25D3, 10-7 M of 25D3, which is within its uppermost physiological concentrations in the bloodstream, induced VDR nuclear import and robustly activated its target gene such as CYP24A1 in the virtual absence of CYP27B1 expression in LNCaP cells. These results indicate that the unconverted 25D3 alone behaved similarly to 1,25D3 in activating CYP24A1 mRNA expression. Our comprehensive microarray analyses verified the bioactivity of 25D3 and we found that 25D3 target gene profiles largely matched those of 1,25D3, while the presence a small subset of 25D3-, or 1,25D3-specific target genes were not excluded. The concentration of 1,25D3 in the culture media after 25D3 treatment with or without siRNA for CYP27B1 mRNA was below the lower limit of the sensitivity measured by ultrasensitive LC/MS/MS method. These results indicated that 25D3 shares bioactivity with 1,25D3 without conversion to the latter at least in some prostate cancer cells.
2017-12-01 | GSE107438 | GEO
Project description:To investigate targets of miR-582-5p that which might participate in the transition to CRPC, we evaluated the gene expression profiles of LNCaP miR-582-5p cells and LNCaP EV cells using DNA microarray analysis.
2014-04-11 | GSE56669 | GEO
Project description:To investigate targets of miR-582-5p that which might participate in the transition to CRPC, we evaluated the gene expression profiles of LNCaP miR-582-5p cells and LNCaP EV cells using DNA microarray analysis. We evaluated the gene expression profiles of LNCaP miR-582-5p cells and LNCaP EV cells using DNA microarray with GeneChipM-BM-. Human Gene 1.0 ST array.
2014-04-11 | E-GEOD-56669 | biostudies-arrayexpress
Project description:We previously encountered regulatory processes where dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone-related protein (PTHrP) gene repression through the estrogen receptor (ER)M-NM-1, but not the androgen receptor (AR) in breast cancer MCF-7 cells. Here, we investigated whether such an aberrant ligand-nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed a functional AR and at negligible levels of ERM-NM-1, and progesterone receptors. Both suppression of PTHrP and activation of the PSA genes were observed after treatment of E2, DHT and R5020. Consistent with the previous notion that the AR in LNCaP cells lost the ligand specificity due to a mutation AR (Thr-Ala877), our study using siRNA targeting each NR revealed that the AR, but not the other NRs, monopolized the role as the mediator of shared hormone-dependent regulation. These results were invariably associated with nuclear translocation of this mutant AR. Microarray of the genes regulated by either DHT, E2 or R5020 downstream of the AR (Thr-Ala877) revealed that more than half genes overlapped in LNCaP cells. Noticeably, AR (wild-type, wt) and AR (Thr-Ala877) were equally responsible for the E2-AR interactions. Fluorescent microscopic experiments demonstrated that both EGFP-AR (wt) and EGFP-AR (Thr-Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Further, a promoter assay revealed that breast cancer MCF-7 and Rv22 cells also exhibited such an aberrant E2-AR (wt) signaling. We postulate entangled interactions between the AR (wt) and E2 in a certain hormone-sensitive cancer cells. Total RNAs from the LNCaP cells transfected with control siRNA (siCT) or siRNA for AR (siAR) transfected LNCaP cells before 24 hr followed by exposed to 10-7M of DHT, E2 or R5020 exposure for another 24 h, respectively, were used.
2014-06-19 | E-GEOD-58615 | biostudies-arrayexpress
Project description:We previously encountered regulatory processes where dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone-related protein (PTHrP) gene repression through the estrogen receptor (ER)α, but not the androgen receptor (AR) in breast cancer MCF-7 cells. Here, we investigated whether such an aberrant ligand-nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed a functional AR and at negligible levels of ERα, and progesterone receptors. Both suppression of PTHrP and activation of the PSA genes were observed after treatment of E2, DHT and R5020. Consistent with the previous notion that the AR in LNCaP cells lost the ligand specificity due to a mutation AR (Thr-Ala877), our study using siRNA targeting each NR revealed that the AR, but not the other NRs, monopolized the role as the mediator of shared hormone-dependent regulation. These results were invariably associated with nuclear translocation of this mutant AR. Microarray of the genes regulated by either DHT, E2 or R5020 downstream of the AR (Thr-Ala877) revealed that more than half genes overlapped in LNCaP cells. Noticeably, AR (wild-type, wt) and AR (Thr-Ala877) were equally responsible for the E2-AR interactions. Fluorescent microscopic experiments demonstrated that both EGFP-AR (wt) and EGFP-AR (Thr-Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Further, a promoter assay revealed that breast cancer MCF-7 and Rv22 cells also exhibited such an aberrant E2-AR (wt) signaling. We postulate entangled interactions between the AR (wt) and E2 in a certain hormone-sensitive cancer cells.
2014-06-19 | GSE58615 | GEO
Project description: Not available
| S-ECPF-GEOD-58615 | biostudies-other
Project description:We report the application of ChIP and RNA sequencing to identify the mechanism whereby stable overexpression of MED19 in androgen-dependent LNCaP cells promotes growth under conditions of androgen deprivation. We determined the MED19 and AR transcriptomes and cistromes in control and MED19 LNCaP cells. We also examined genome-wide H3K27 acetylation in both the absence and presence of androgens. We found that MED19 overexpression selectively alters AR occupancy, H3K27 acetylation, and gene expression. Under conditions of androgen deprivation, genes regulated by MED19 correspond to genes regulated by ELK1, a transcription factor that binds the AR N-terminus to induce select AR target gene expression and proliferation. This study provides important insight into the mechanisms of prostate cancer cell growth under low androgen, and underscores the importance of the MED19 in this process.
2021-01-20 | GSE161170 | GEO
Project description:Purpose: To detect the diffirential expressed genes in LNCaP cells transfected with VIM-AS1 overexression vetor and control pcDNA3.1 vector Method: Transcriptome sequencing was sued to detect the diffirential expressed genes in LNCaP cells transfected with VIM-AS1 overexression vetor and control pcDNA3.1 vector Results :We performed transcriptome sequencing to identify the target genes in VIM-AS1 overexpressed LNCaP cells and normal control. 67 genes were found statistically up-regulated more than two-fold and 187 genes were found statistically down-regulated more than two-fold in VIM-AS1 overexpressed LNCaP cells Conclusion:Our study represents the first detailed analyasis of transcriptomes in LNCaP cells with VIM-AS1 overexpression and control cells.
2022-12-08 | GSE220250 | GEO
Project description:Transcriptome profiles of alternative MED19 LNCaP and control LNCaP cells cultured under androgen deprivation with vehicle or R1881
| PRJNA676100 | ENA
Project description:Comparison of miRNA expression profiles directly comparing PC3 cells to LNCaP cells using unamplified and amplified miRNA. Keywords: Expression profiling of hormone sensitive vs. insensitive prostate cancer cell lines and evaluation of amplification fidelity
2006-04-05 | GSE4572 | GEO