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Series GSE205348 Query DataSets for GSE205348
Status Public on Jun 08, 2023
Title Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The first line of therapy for advanced prostate cancer (PCa) is androgen-deprivation therapy (ADT) through surgical or chemical castration; however, in the majority of cases, tumors relapse in a hormone refractory or castration resistant prostate cancer (CRPC) form. Once the PCa has recurred in CRPC form, it progresses to a highly aggressive disease with frequent metastasis and poses an increased risk of morbidity and death. This study shows that the loss of PP2Acα methylation in enzalutamide (Enza)-resistant CRPC cells plays a central role in imparting the resistant to the cancer cells by stabilizing the interaction of MED1, BRD4, and AR associated transcriptional complex, thereby amplifying the oncogenic AR transcriptional output through chromatin re-modulatory mechanism. Further, this study demonstrates that targeting the PP2ACα regulatory mechanisms or its downstream epigenetic effectors/mechanisms abolish the enzalutamide-resistance phenotype, thus paving the way for the development of more effective therapeutics to curtail mCRPC. The below given experiments validate the above findings.
 
Overall design LNCaP enzalutamide-resistant (LNCaP-MDVR) cell line was generated by culturing the parental LNCaP cells in presence of enzalutamide for 4-6 months. The comparison of the two cell lines in terms of MED1 and AR chromatin recruitment was performed upon DMSO or ARD-69 or DT-061 treatment. LNCaP cells stably over-expressing LacZ and leucine carboxyl methyltransferase 1 (LCMT1) were prepared and used to study the differential chromatin binding of MED1 and AR.
Web link https://www.nature.com/articles/s41467-023-40760-6
 
Contributor(s) Asangani I, Rasool RU, Alhusayan M
Citation(s) 37644036
Submission date Jun 02, 2022
Last update date Sep 07, 2023
Contact name Irfan Asangani
E-mail(s) asangani@upenn.edu
Phone 215-746-8780
Organization name University of Pennsylvania
Department Cancer Biology
Lab Asangani Lab
Street address 421 Curie Blvd
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (11)
GSM6210763 LNCAP-EnzaR_DMSO_AR
GSM6210764 LNCAP-EnzaR_DMSO_MED1
GSM6210765 LNCAP-EnzaR_ARD69_AR
Relations
BioProject PRJNA844558

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE205348_RAW.tar 3.3 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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