Disease relevance of Pten

• Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN [1].
• Hereditary mutation of PTEN causes tumor-susceptibility diseases such as Cowden disease [2].
• In contrast to the mild effects of removing HM site phosphorylation at normal levels of PI3K activity, loss of TORC2 activity strongly inhibited hyperplasia caused by elevated pathway activity, as in mutants of the tumor suppressor PTEN [3].

High impact information on Pten

• Pten is thus indispensable for normal cardiovascular morphogenesis and post-natal angiogenesis, including tumor angiogenesis [2].
• PTEN is an important tumor suppressor gene [2].
• Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway [4].
• Here we show that the highly evolutionarily conserved Drosophila PTEN homolog, DPTEN, suppresses hyperplastic growth in flies by reducing cell size and number [4].
• Surprisingly, although DPTEN does not generally affect cell fate determination, it does appear to regulate the subcellular organization of the actin cytoskeleton in multiple cell types [4].

Chemical compound and disease context of Pten

• We link early renal hypertrophy with significant reduction in PTEN expression in the streptozotocin-induced diabetic kidney cortex and glomeruli, concomitant with activation of Akt [1].

Biological context of Pten

• Furthermore, we present biochemical and genetic evidence that loss of the homolog of the tumor suppressor gene, Pten, results in increased PtdInsP(3) levels and that these increased levels are sufficient to compensate for the complete loss of the Insulin/insulin-like growth factor receptor function [5].
• Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA [6].
• We find that loss of the IIS signalling antagonist PTEN, which stimulates cell growth in most developing tissues, produces a very different phenotype in nurse cells, inducing formation of highly enlarged lipid droplets [7].
• Mice mutant for PTEN die at early embryonic stages and the mutant embryonic fibroblasts display decreased sensitivity to cell death [8].
• Furthermore we have performed genetic epistasis tests to demonstrate that in Drosophila, PI3'K, PTEN and Akt comprise a signaling cassette that is utilized during multiple stages of development [9].

Anatomical context of Pten

• Two endogenous PTEN transcripts with 5'-UTRs of 193 and 109 bases were found in DU145 and H226 cell lines [10].
• RESULTS: We show that in photoreceptors Bazooka (D-Par3) recruits the tumor suppressor lipid phosphatase PTEN to developing cell-cell junctions (Zonula Adherens, za). za-localized PTEN controls the spatially restricted accumulation of optimum levels of the lipid PtdIns(3,4,5)P3 within the apical membrane domain [11].
• Second, neither exogenous ecdysone nor overexpression of PTEN, a silencer of PI3K signaling, restored fusion of autophagosomes with lysosomes in the fat body of dor mutants [12].

Associations of Pten with chemical compounds

• We demonstrate that this rescue of the PTEN-induced eye size phenotype requires cysteine-218 in the C2 domain of PTEN [13].
• PTEN is an important regulator of phosphoinositide turnover that antagonizes the activity of PI3-kinase [14].
• Similarly, exposure of mesangial cells to high concentrations of glucose also decreased PTEN expression and its phosphatase activity, resulting in increased Akt activity [1].

Physical interactions of Pten

• We show that the lipid phosphatase PTEN directly binds to Baz in vitro and in vivo, and colocalizes with Baz in the apical cortex of epithelia and neuroblasts [14].

Regulatory relationships of Pten

• Akt is regulated by phosphatidylinositol 3-OH kinase (PI3'K) signaling and has shown to be hyperactivated through the loss of the PTEN tumor suppressor [9].

Other interactions of Pten

• The conserved PI3'K/PTEN/Akt signaling pathway regulates both cell size and survival in Drosophila [9].

Analytical, diagnostic and therapeutic context of Pten

• From these data, we propose that DPTEN has a complex role in regulating tissue and body size [4].

References