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Series GSE178406 Query DataSets for GSE178406
Status Public on Feb 28, 2022
Title The Androgen Receptor: A Therapeutic Target In Desmoplastic Small Round Cell Sarcoma
Organism Homo sapiens
Experiment type Protein profiling by protein array
Summary Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that AR-directed antisense oligonucleotides (AR-ASO) block 5-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduced xenograft tumor burden. RPPA analysis was performed to elucidate how AR signaling regulates cellular programs. To gain a preliminary understanding of the short-term pharmacodynamic effects of AR suppression, a group of JN-DSRCT xenografts was collected 10 days into their AR-ASO treatment for analysis by RPPA to assess early compensatory pharmacodynamic changes. Its blockade has long been of interest in managing prostate cancer, where a compensatory increase in AKT signaling has been reported following AR inhibition. Therefore, these results collectively validate another proof of concept of AR-based antisense activity in DSRCT and suggest a clinical path forward since the AR-ASO (AZD5312) was safe, and often effective, in PC patients (NCT03300505). Our findings have immediate clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.
 
Overall design DSRCT xenograft or PDX animal tumors for RPPA analysis were snap-frozen. Next, protein extraction from xenograft/PDX tumors was performed by homogenizing approximately 10 mg of frozen tissue in 500 μL of the lysis buffer using an electric tissue homogenizer (PRO Scientific). The homogenized tumors were incubated at +4°C for 2 hours to complete their dissociation and lysis. Altogether, the total lysed proteins from tumors were collected after centrifugation, quantified using BCA protein assay kit (Thermo Fisher Scientific), and stored at -80°C until further analyses. Lysates were processed, spotted onto nitrocellulose-coated FAST slides, probed with 377 validated primary antibodies, and detected using a DakoCytomation-catalyzed system with secondary antibodies. MicroVigene software program (VigeneTech) was used for automated spot identification, background correction, and individual spot-intensity determination. Expression data as Log2 values was normalized for possible unequal protein loading, taking into account the signal intensity for each sample for all antibodies tested.
 
Contributor(s) Lamhamedi-Cherradi S, Menegaz BA, Ludwig JA
Citation(s) 35650195
Submission date Jun 17, 2021
Last update date Jun 21, 2022
Contact name Joseph A. Ludwig
E-mail(s) jaludwig@mdanderson.org
Phone 713-792-4265
Organization name UT-MD-Anderson Cancer Center
Department Sarcoma Medical Oncology
Lab Sarcoma Medical Oncology
Street address 4SCR2-1042 1901 East Rd
City Houston
State/province Texas
ZIP/Postal code 77054
Country USA
 
Platforms (1)
GPL30286 The Androgen Receptor: A Therapeutic Target In Desmoplastic Small Round Cell Sarcoma
Samples (32)
GSM5390394 JN-DSRCT-Xenograft-Control ASO#1063
GSM5390395 JN-DSRCT-Xenograft-Control ASO#1068
GSM5390396 JN-DSRCT-Xenograft-Control ASO#1069
Relations
BioProject PRJNA738891

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
GSE178406_raw_data.txt.gz 75.0 Kb (ftp)(http) TXT
Processed data included within Sample table

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