Identification of KMT5A regulated genes in prostate cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233350 | GEO | 2023/05/26
REPOSITORIES: GEO
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Project description:In this study the development of androgen independence in a cell model of disease was selected as a mirror of to the events at play in the development of Castrate Resistant Prostate Cancer in-vivo. LNCaP cells which are androgen dependent and androgen independent sublines; LNCaP-Abl and LNCaP-Abl-Hof were subject to extensive fractionation by 1-D SDS PAGE and accurate mass-high resolution mass spectrometry (Q Exactive) to identify proteins whose expression was changes significantly in response to androgen independent growth.
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Project description:We generated and characterized an androgen-independent LNCaP-AI cell line by long-term culture of androgen-dependent LNCaP cells in RPMI-1640 medium containing charcoal-stripped serum. This approach used to generate the line mimics the castration resistant condition for treating prostate cancer, supporting the relevance of the LNCAP-AI cell line to Castration Resistant Prostate Cancer.
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Project description:High levels of GLI (GLI1 and GLI2) mRNA and GLI luciferase reporter activity were detected in the androgen independent prostate cancer cell lines DU145 and PC-3 compared to the androgen-dependent LNCaP prostate cancer cell line. Subsequently, we observed that ectopic GLI1 promoted hormone independence in LNCaP cells (LNCaP-GLI1). We compared the gene expression profile of LNCaP-pBP (empty vector), LNCaP-GLI1, DU145, and PC-3 cells globally as well as to identify GLI1-regulated genes that may contribute to hormone independence.
2011-02-13 | GSE27231 | GEO
Project description:High levels of GLI (GLI1 and GLI2) mRNA and GLI luciferase reporter activity were detected in the androgen independent prostate cancer cell lines DU145 and PC-3 compared to the androgen-dependent LNCaP prostate cancer cell line. Subsequently, we observed that ectopic GLI1 promoted hormone independence in LNCaP cells (LNCaP-GLI1). We compared the gene expression profile of LNCaP-pBP (empty vector), LNCaP-GLI1, DU145, and PC-3 cells globally as well as to identify GLI1-regulated genes that may contribute to hormone independence. RNA was harvested and analysed from LNCap-pBP (control/reference sample), LNCaP-GLI1, DU145 and PC-3 cells
2011-02-13 | E-GEOD-27231 | biostudies-arrayexpress
Project description:To further determine the gene expression in the castration resistant condition for treating PCa, we generated and characterized an androgen-independent LNCaP-AI cell line by long-term culture of androgen-dependent LNCaP cells in RPMI-1640 medium containing charcoal-stripped serum.
2018-12-22 | GSE124291 | GEO
Project description:It has been well established that the transcription factor androgen receptor (AR) is obligatory for prostate cancer (PCa) development and progression, but the precise role of the AR in these processes is still unclear. To dissect the role of AR in shaping the transcriptome of prostate cancer cells, RNA-seq data were obtained from AR-positive LNCaP cells treated with various regimens to manipulate endogenous AR signaling. LNCaP cells were cultured in normal medium containing fetal bovine serum (FBS) to represent an androgen-dependent (AD) growth state. To mimic the clinical androgen-deprivation-therapy (ADT) settings, cells were grown for 4 days in conditions of either depletion of androgen (i.e., medium containing charcoal:dextran stripped fetal bovine serum (CDSS)) or the presence of AR antagonist Enzalutamide (MDV3100, 10 μM) to represent androgen-independent (AI) growth states. Aside from the pharmaceutical modulations, we also utilized siRNA to knockdown AR. To examine the direct effects of AR signaling on gene transcription and splicing, cells were primed with CDSS for 3 days followed by treatment of 10nM dihydrotestosterone (DHT) for 8-9 hrs. Deep sequencing of rRNA-depleted total RNAs was performed in biological duplicates on abovementioned LNCaP cultures.
2020-03-04 | GSE114052 | GEO
Project description:Identification of KMT5A regulated genes in prostate cancer
| PRJNA975927 | ENA
Project description:Increasing evidence indicates that minor subpopulations intrinsic to androgen-independence are present in prostate cancer cells, poised to become clonal dominance under prolonged androgen-deprivation selection. To stratify different subpopulations, we conduct transcriptome profiling of 144 single LNCaP prostate cancer cells treated and untreated with androgen after cell cycle synchronization. At least eight subpopulations of LNCaP cells are identified, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation. One subpopulation displays stem-like features, the advanced growth of which depends more on enhanced expression of 10 cell cycle-related genes and less on androgen-dependent signaling. Concordant upregulation of these genes appears to be linked to recurrent prostate cancers and can be used for early detection of tumors that subsequently develop androgen independence. Moreover, this single-cell approach provides a better understanding of how cancer cells respond heterogeneously to androgen-deprivation therapies and to reveal which subpopulations are resistant to this treatment.
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Project description:Following androgen ablation therapy (AAT), the vast majority of prostate cancer patients develop treatment resistance with a median time of 18-24 months to disease progression. To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI). We discovered alterations in gene expression for a host of molecules associated with promoting prostate cancer cell growth and survival, regulating cell cycle progression, apoptosis and adrenal androgen metabolism, in addition to AR co-regulators and markers of neuroendocrine disease. These findings illustrate the complexity and unpredictable nature of cancer cell biology and contribute greatly to our understanding of how prostate cancer cells likely survive AAT. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the cellular response to androgen deprivation; it provides a more dynamic illustration of those genes which contribute to disease progression in addition to specific genes which constitute a malignant androgen-independent phenotype. In conclusion, it is of great importance that we employ new approaches, such as the one proposed here, to continue exploring the cellular mechanisms of therapy resistance and identify promising targets to improve cancer therapeutics. Experiment Overall Design: To identify molecular targets that aid in prostate cancer cell survival and contribute to the androgen independent phenotype, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and during the emergence of highly proliferative, androgen-independent prostate cancer cells (LNCaP-AI).
2008-04-07 | E-GEOD-8702 | biostudies-arrayexpress
Project description:Despite the success of the aromatase inhibitors (AIs) in treating estrogen receptor positive breast cancer, 15-20% of patients receiving adjuvant AIs will relapse within 5-10 years of treatment initiation. Long term estrogen deprivation (LTED) of breast cancer cells in culture has been successfully used to mimic AI-induced estrogen depletion to dissect mechanisms of AI resistance. However, we hypothesized that a subset of patients receiving AI therapy may maintain low circulating concentrations of estrogens that influence the development of endocrine resistance. We sought to expand established LTED models to account for these observations. MCF-7 cells were grown in medium with charcoal stripped serum supplemented with defined concentrations of E2 or the estrogenic androgen metabolite 3βAdiol. Cells were selected in the EC10 and EC90 of E2 or 3βAdiol, or estrogen deprived. Estrogen-independence was evaluated during selection by assessing cell growth in the absence or presence of E2 or 3βAdiol. Following >7 months of selection, estrogen-independence developed in estrogen-deprived cells and cells maintained in low concentrations of steroid hormone. Functional analyses demonstrated that estrogen-deprived and low-steroid selected cells developed estrogen-independence via unique mechanisms, independent and dependent of ERα, respectively. Estrogen-independent growth in low-steroid selected cells could be blocked by kinase inhibitors. However, these cells were completely resistant to kinase inhibition in the presence of low steroid hormone concentrations. These data offer a novel perspective on the development of resistance to AI therapy, and may yield novel approaches to treat AI-resistant tumors. MCF-7 cells were selected for >7months in IMEM+10% Charcoal Stripped FBS, supplmented with defined steroid hormone conditions. Following outgrowth of estrogen-independent cells, cell lines were grown in estrogen-free conditions and gene expression analysis was performed to identify drivers of estrogen-independent growth. Cells were assessed in biological triplicates.
2012-03-29 | E-GEOD-33287 | biostudies-arrayexpress