Fig. 5: Inverse relationship between AKT2 and SMAD4 expression.
From: PTEN-regulated PI3K-p110 and AKT isoform plasticity controls metastatic prostate cancer progression
A The relative levels of AKT1, AKT2, and SMAD4 RNA levels vs. PTEN status in human PC cell lines assessed in NCBI GEO dataset GDS1699. Heat map of RNA-seq data comparing Smad4 and Akt2 RNA levels (B) or Smad4 protein levels (C) from Pten/Rb- and Akap12/Rb-null (KO) prostate lesions. Knockdown of Akt2 (D), but not Akt1 or Akt3 (E) in T402 cells correlates with increased Smad4. F SMAD4 knockdown in LNCaP and 22Rv1 (analyzed by IB in the top panels) correlates with decreased chemotaxis (bottom panels). Numbers under IBs in panels C-F describe relative SMAD4 protein levels (vs. protein loading controls). **P ≤ 0.01, ****P ≤ 0.0001. G IB analysis for SMAD4 or β-Actin in T402, LNCaP or 22Rv1 cell pairs isogenic for PTEN that were grown in 2D vs. 3D conditions. H Treatment (24 h) with AKT2i induces SMAD4 in LNCaP but not in LNCaP[PTEN] cells. I Induction of SMAD4 by AKT2i in LNCaP correlates with decreased levels of AKT substrates, assessed by IB using canonical AKT substrate motif Ab (RxxSpo/Tpo), but no changes in total AKT1 or AKT2 protein levels.
