NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE43881 Query DataSets for GSE43881
Status Public on Jan 30, 2013
Title HIPK2 and MED19 are new regulators of androgen receptor in prostate cancer cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The androgen receptor (AR) is a mediator of both androgen-dependent and castration- resistant prostate cancers. Identification of cellular factors affecting AR transcriptional activity could in principle yield new targets that reduce AR activity and combat prostate cancer, yet a comprehensive analysis of the genes required for AR-dependent transcriptional activity has not been determined. Using an unbiased genetic approach that takes advantage of the evolutionary conservation of AR signaling, we have conducted a genome-wide RNAi screen in Drosophila cells for genes required for AR transcriptional activity and applied the results to human prostate cancer cells. We identified 45 AR-regulators, which include known pathway components and genes with functions not previously linked to AR regulation, such as HIPK2 (a protein kinase) and MED19 (a subunit of the Mediator complex). Depletion of HIPK2 and MED19 in human prostate cancer cells decreased AR target gene expression and, importantly, reduced the proliferation of androgen-dependent and castration-resistant prostate cancer cells. We also systematically analyzed additional Mediator subunits and uncovered a small subset of Mediator subunits that interpret AR signaling and affect AR-dependent transcription and prostate cancer cell proliferation. Importantly, targeting of HIPK2 by an FDA approved kinase inhibitor phenocopied the effect of depletion by RNAi and reduced the growth of AR-positive, but not AR negative, treatment-resistant prostate cancer cells. Thus, our screen has yielded new AR regulators including drugable targets that reduce the proliferation of castration-resistant prostate cancer cells.
HIPK2 and MED19 were identified via a genome-wide RNAi screen as new androgen receptor (AR) reulators. Our goal in performing this microarray was to identify the gene regulated by HIPK2 and MED19 in a late stage prostate cancer cell line (LNCaP-abl), and to see what genes are in common with known genes to be regulated by AR, and what genes are unique to HIPK2 or MED19.
 
Overall design Knockdown of HIPK2 and MED19 was tested in LNCaP-abl cells against control. Each was performed in duplicates. Six samples were analyzed
 
Contributor(s) Imberg K, Greenfield A
Citation(s) 23403032
Submission date Jan 29, 2013
Last update date Mar 25, 2019
Contact name Michael Garabedian
E-mail(s) michael.garabedian@nyumc.org
Phone 212 263-7662
Fax 212 263-8276
URL http://microbiology-parasitology.med.nyu.edu/node/122
Organization name NYU School of Medicine
Department Microbiology
Street address 550 First Avenue
City New York
State/province NY
ZIP/Postal code 10016
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (6)
GSM1072825 LNCaP-abl_siHIPK2_2
GSM1072826 LNCaP-abl_siControl_1
GSM1072827 LNCaP-abl_siControl_2
Relations
BioProject PRJNA187993

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
GSE43881_RAW.tar 30.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap