|
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)
|
|
Relations |
BioProject |
PRJNA1013326 |