Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA151417 | ENA |
REPOSITORIES: ENA
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Project description:Aberrant androgen receptor (AR)-mediated transcription is a critical driver in progression of human prostate cancer. It's known that different doses of androgens can elicit differential transcriptional and proliferative responses in prostate-tumor cells. Here, we set out to examine the androgenic regulation of glycoprotein expression in the membrane fraction of prostate-tumor cells that could serve as mediators or markers of androgen-induced proliferative responses observed in prostate-tumor cells. A bioanalytical workflow involving lectin-affinity chromatography and label-free quantitative mass spectrometry was used to identify androgen-sensitive glycomembrane protein expression associated with androgen-mediated proliferation. This study would facilitate the identification of surface membrane proteins involved in androgen-mediated proliferation and provide potential therapeutic targets in the detection treatment of proliferation prostate-tumors.
2022-03-01 | PXD002913 | Pride
Project description:MicroRNAs (miRNAs) function as regulators of cancer progression as they modulate different cellular processes. The objective of this study is to demonstrate a multi-dimensional function of miR-30e through regulating genes involved in various signaling pathways including androgen receptor signaling. miR-30e targets androgen receptor mRNA and functions as a tumor suppressor. We noted loss of miR-30e expression in prostate tumors and restored expression of miR-30e led to cell cycle arrest, induction of apoptosis, improved drug sensitivity in prostate cancer cells, and reduced tumor progression in prostate cancer xenograft models. To understand the tumor suppressor function of miR-30e on a global scale, we performed total RNA-sequence analysis upon overexpression of miR-30e in a prostate cancer cell line 22Rv-1, which expresses a splice variant of androgen receptor and represents an androgen-independent and drug-resistant form of prostate cancer.qRT-PCR validation of RNA-sequencing data supports our in vitro study showeing differential expression of genes involved in cell cycle progression, apoptosis and ubiquitination upon expression of miR-30e in prostate cancer cells.
2022-08-31 | GSE188345 | GEO
Project description:Following extensive treatment with androgen receptor (AR) pathway inhibitors, a significant number of metastatic prostate cancer develop treatment resistance, and approximately 20% of these castration-resistant prostate cancers (CRPC) transdifferentiate, at least partially, into neuroendocrine (NE) prostate cancer (NEPC).In human cancer, FOXA2 is highly expressed in most of NEPC and a small portion of CRPC patients, has been suggested as a marker of NEPC and elevated in other NE lineage cancers including SCLC. In addition, preclinical studies demonstrated that Foxa2 is required for NEPC tumor growth and metastasis in TRAMP mouse model and associated with NEPC transformation in Pten, Trp53, and Rb1 triple knockout mouse model. However, whether FOXA2 is an essential driver of NEPC, and the underlying mechanism in shaping epigenetic landscape of NEPC is largely unknown.
2025-06-12 | PXD061127 | Pride
Project description:Following extensive treatment with androgen receptor (AR) pathway inhibitors, a significant number of metastatic prostate cancer develop treatment resistance, and approximately 20% of these castration-resistant prostate cancers (CRPC) transdifferentiate, at least partially, into neuroendocrine (NE) prostate cancer (NEPC).In human cancer, FOXA2 is highly expressed in most of NEPC and a small portion of CRPC patients, has been suggested as a marker of NEPC and elevated in other NE lineage cancers including SCLC. In addition, preclinical studies demonstrated that Foxa2 is required for NEPC tumor growth and metastasis in TRAMP mouse model and associated with NEPC transformation in Pten, Trp53, and Rb1 triple knockout mouse model. However, whether FOXA2 is an essential driver of NEPC, and the underlying mechanism in shaping epigenetic landscape of NEPC is largely unknown.
2025-06-12 | PXD061080 | Pride
Project description:TMEFF2 is an androgen regulated transmembrane protein mainly restricted to brain and prostate, that functions as a tumor suppressor in prostate cancer (PCa). Studies using publically available prostate cancer (PCa) datasets, reveal changes in the expression of TMEFF2 with disease stage, supporting an important role of TMEFF2 in this disease. However, the role of TMEFF2 in the biology and pathogenesis of PCa is still unknown. Using a transgenic TMEFF2 mouse, we have demonstrated that TMEFF2 overexpression modulates prostate branching morphogenesis, and androgen regulated process, during prostate regeneration. We hypothesized that TMEFF2 may have a regulatory function within androgen signaling that could explain its role in PCa. To better understand its function in androgen signaling and PCa, we compared the transcriptome of LNCaP prostate cancer cells transduced with control shRNA and shRNA targeting TMEFF2 in the presence and absence of dihydrotestosterone (DHT). The results indicated that globally, there is a significant interaction between the effects of DHT and shTMEFF2. Of the 519 genes with significant gene expression changes after DHT treatment of Scramble control cells, 208 (40%) had significant differential expression when the shTMEFF2 +DHT group was compared to Scramble +DHT group, including numerous androgen activated and androgen repressed genes.
2019-04-01 | GSE117180 | GEO
Project description:Long noncoding RNAs (lncRNAs) have recently been associated with the development and progression of a variety of human cancers. However, to date, the interplay between known oncogenic or tumor suppressive events and lncRNAs has not been well described. Here the novel lncRNA, Prostate Cancer-Associated Transcript 29 (PCAT29), is characterized along with its relationship to the androgen receptor (AR). PCAT29 is suppressed by dihydrotestosterone (DHT) and up-regulated upon castration therapy in a prostate cancer xenograft model. PCAT29 knockdown significantly increased proliferation and migration of prostate cancer cells, while PCAT29 overexpression conferred the opposite effect and suppressed growth and metastases of prostate tumors in chick chorioallantoic membrane (CAM) assays. Finally, in prostate cancer patient specimens, low PCAT29 expression correlated with poor prognostic outcomes. Taken together, these data expose PCAT29 as an androgen regulated tumor suppressor in prostate cancer PCAT29 was knockdown using shRNA in two prostate cancer cell lines VCaP and LNCaP.
2014-07-01 | E-GEOD-58397 | biostudies-arrayexpress
Project description:Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers.
2007-05-04 | E-SMDB-4028 | biostudies-arrayexpress
Project description:Although the vital role of the androgen receptor (AR) has been well demonstrated in primary prostate cancers, its role in the androgen-insensitive prostate cancers still remains unclear. Here, we used a small hairpin RNA approach to directly assess AR activity in prostate cancer cells. Reduction of AR expression in the two androgen-sensitive prostate cancer cell lines, LNCaP and LAPC4, significantly decreased AR-mediated transcription and cell growth. Intriguingly, in two androgen-insensitive prostate cell lines, LNCaP-C42B4 and CWR22Rv1, knockdown of AR expression showed a more pronounced effect on AR-induced transcription and cell growth than androgen depletion. Using cDNA microarrays, we also compared the transcriptional profiles induced by either androgen depletion or AR knockdown. Although a significant number of transcripts appear to be regulated by both androgen depletion and AR knockdown, we observed a subset of transcripts affected only by androgen depletion but not by AR knockdown, and vice versa. Finally, we demonstrated a direct role for AR in promoting tumor formation and growth in a xenograft model. Taken together, our results elucidate an important role for the AR in androgen-insensitive prostate cancer cells, and suggest that AR can be used as a therapeutic target for androgen-insensitive prostate cancers. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Computed
2007-08-08 | E-GEOD-7585 | biostudies-arrayexpress
Project description:Purpose: Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) is effective against prostate cancer (PCa), but all patients relapse eventually. Poor understanding of the underlying resistance mechanisms represents a key barrier to development of more effective RLT. We investigate the proteome and phosphoproteome in a mouse model of PCa to identify signaling adaptations triggered by PSMA-RLT.
Experimental Design: Therapeutic efficacy of PSMA-RLT was assessed by tumor volume measurements, time to progression, and survival in C4-2 or C4-2 TP53-knockout tumor-bearing Nod scid gamma mice. Two days post-RLT, the (phospho)proteome was analyzed by mass spectrometry.
Results: PSMA-RLT significantly improved disease control in a dose-dependent manner. (Phospho)proteomic datasets revealed activation of genotoxic stress response pathways, including deregulation of DNA damage/replication stress response, TP53, androgen receptor, PI3K/AKT, and MYC signaling. C4-2 TP53-knockout tumors were less sensitive to PSMA-RLT than parental counterparts, supporting a role for TP53 in mediating RLT responsiveness.
Conclusions: We identified signaling alterations that may mediate resistance to PSMA-RLT in a PCa mouse model. Our data enable the development of rational synergistic RLT-combination therapies to improve outcomes for PCa patients.
2020-11-04 | MSV000086408 | MassIVE
Project description:Androgen receptor (AR) signalling pathway plays an important role in carcinogenesis and development of prostate cancer. The involvement of microRNA (miRNA) in this process is still largely unknown. In this study, we performed a matched miRNA-mRNA time-course expression profiling to reveal androgen response in hormone-sensitive prostate cancer cells.We introduced novel statistics Response Score (RS) and Modulation Score (MS) to identify significant androgen-regulated target genes and miRNA-modulated target mRNAs. Based on the analysis, we found several novel androgen-regulated targets, which had significant androgen response in expression pattern, and were highly enriched in predicted androgen responsive elements (AREs). AR-bindings to these AREs were validated with ChIP assay. Furthermore, a set of target mRNAs involved in crucial processes of tumor progression were identified to be significantly regulated by these miRNAs. Therefore, a miRNA-mediated androgen signalling network was inferred, including three novel feedback mechanisms for AR self-modulation. In conclusion, our study provides new approaches to further miRNA regulation research and contributes novel findings into miRNA-mediated pathological effects in prostate cancer. Total RNA obtained from androgen dihydrotestosterone (DHT) subjected to LNCaP cells in vitro at 20min, 40min, 1h, 2h, 4h, 8h, 16h, 24h and 48h, compared to the control at 0h.
2011-12-31 | E-GEOD-21245 | biostudies-arrayexpress