NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE242387 Query DataSets for GSE242387
Status Public on Nov 01, 2023
Title PTEN regulated PI3K-p110 and AKT isoform plasticity controls metastatic prostate cancer progression
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary PTEN loss, one of the most frequent mutations in prostate cancer (PC), is presumed to drive disease progression through AKT activation. However, two transgenic PC models with Akt activation plus Rb loss exhibited different metastatic development: Pten/RbPE:-/- mice produced systemic metastatic adenocarcinomas with high AKT2 activation, whereas RbPE:-/- mice deficient for the Src-scaffolding protein, Akap12, induced high-grade prostatic intraepithelial neoplasias and indolent lymph node dissemination, correlating with upregulated phosphotyrosyl PI3K-p85α. Using PC cells isogenic for PTEN, we show that PTEN-deficiency correlated with dependence on both p110β and AKT2 for in vitro and in vivo parameters of metastatic growth or motility, and with downregulation of SMAD4, a known PC metastasis suppressor. In contrast, PTEN expression, which dampened these oncogenic behaviors, correlated with greater dependence on p110α plus AKT1. Our data suggest that metastatic PC aggressiveness is controlled by specific PI3K/AKT isoform combinations influenced by divergent Src activation or PTEN-loss pathways.
 
Overall design Four high-grade PIN lesions from Akap12/Rb-null mice (Pr_14273, Pr_14345, Pr_14354, Pr_14433). Two PC tumors from Pten/Rb-null mice (PT_T57, PT_173PT) are available in GSE90891 as samples GSM2417050 and GSM2417051, respectively.
 
Contributor(s) Miller KA, Gelman IH
Citation(s) 37875657
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 CA094108 PKC/PKA Regulation in Prostate Cancer by SSeCKS/Gravin/AKAP12 HEALTH RESEARCH INC. AND ROSWELL PARK CANCER INSTITUTE Irwin H. Gelman
R01 CA234162 NOTCH signaling controls transformation to androgen independent neuroendocrine prostate cancer HEALTH RESEARCH INC. AND ROSWELL PARK CANCER INSTITUTE David W. Goodrich
U24 CA274159 Coordinating and Data Management Center for Acquired Resistance to Therapy Network HEALTH RESEARCH INC. AND ROSWELL PARK CANCER INSTITUTE David W. Goodrich
P30 CA016056 Cancer Data Talks in AI/AN/Native Hawaiian and Indigenous Landscapes HEALTH RESEARCH INC. AND ROSWELL PARK CANCER INSTITUTE Candace S Johnson
Submission date Sep 05, 2023
Last update date Jan 06, 2025
Contact name Henry G. Withers
E-mail(s) henry.withers@roswellpark.org
Organization name Roswell Park Comprehensive Cancer Center
Department Biostatistics and Bioinformatics
Street address Elm and Carlton Streets
City Buffalo
State/province New York
ZIP/Postal code 14263
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (4)
GSM7761982 Pr_14273
GSM7761983 Pr_14345
GSM7761984 Pr_14433
Relations
BioProject PRJNA1013326

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
GSE242387_raw_counts_all_samples.csv.gz 201.9 Kb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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