biostudies-literatureFernandez-Marcos PJNIAID NIH HHS12962-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC2722271biostudies-literatureUnknown106(31)Prostate cancer is one of the most common neoplasias in men. The tumor suppressor Par-4 is an important negative regulator of the canonical NF-kappaB pathway and is highly expressed in prostate. Here we show that Par-4 expression is lost in a high percentage of human prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss. Par-4 null mice, similar to PTEN-heterozygous mice, only develop benign prostate lesions, but, importantly, concomitant Par-4 ablation and PTEN-heterozygosity lead to invasive prostate carcinoma in mice. This strong tumorigenic cooperation is anticipated in the preneoplastic prostate epithelium by an additive increase in Akt activation and a synergistic stimulation of NF-kappaB. These results establisProceedings of the National Academy of Sciences of the United States of AmericaSimultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-kappaB activation and invasive prostate carcinoma.PMC2722271R01 AI072581R01-AI072581Moscat JJoshi JCastilla EAAbu-Baker SSaez CCollado MPalacios JGalvez AMoreno-Bueno GFernandez-Marcos PJDiaz-Meco MTCanamero MLeitges MSerrano MfalseSimultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-kappaB activation and invasive prostate carcinoma.Prostate cancer is one of the most common neoplasias in men. The tumor suppressor Par-4 is an important negative regulator of the canonical NF-kappaB pathway and is highly expressed in prostate. Here we show that Par-4 expression is lost in a high percentage of human prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss. Par-4 null mice, similar to PTEN-heterozygous mice, only develop benign prostate lesions, but, importantly, concomitant Par-4 ablation and PTEN-heterozygosity lead to invasive prostate carcinoma in mice. This strong tumorigenic cooperation is anticipated in the preneoplastic prostate epithelium by an additive increase in Akt activation and a synergistic stimulation of NF-kappaB. These results establis2009-01-01T00:00:00Z2009 Aug2025-04-05T15:10:10.129Z2019-03-27T00:24:02ZS-EPMC27222711947046310.1073/pnas.0813055106