| First Author | Nguyen AH | Year | 2013 |
| Journal | Hum Mol Genet | Volume | 22 |
| Issue | 12 | Pages | 2400-10 |
| PubMed ID | 23428429 | Mgi Jnum | J:198151 |
| Mgi Id | MGI:5495595 | Doi | 10.1093/hmg/ddt088 |
| Citation | Nguyen AH, et al. (2013) Gata3 antagonizes cancer progression in Pten-deficient prostates. Hum Mol Genet 22(12):2400-10 |
| abstractText | Loss of the tumor suppressor PTEN is a common occurrence in prostate cancer. This aberration leads to the ectopic activation of the PI3K-Akt pathway, which promotes tumor growth. Here, we show that the transcription factor Gata3 is progressively lost in Pten-deficient mouse prostate tumors as a result of both transcriptional down-regulation and increased proteasomal degradation. To determine the significance of this loss, we used conditional loss- and gain-of-function approaches to manipulate Gata3 expression levels in prostate tumors. Our results show that Gata3 inactivation in Pten-deficient prostates accelerates tumor invasion. Conversely, enforced expression of GATA3 in Pten-deficient tissues markedly delays tumor progression. In Pten-deficient prostatic ducts, enforced GATA3 prevented Akt activation, which correlated with the down-regulation of Pik3cg and Pik3c2a mRNAs, encoding respectively class I and II PI3K subunits. Remarkably, the majority of human prostate tumors similarly show loss of active GATA3 as they progress to the aggressive castrate-resistant stage. In addition, GATA3 expression levels in hormone-sensitive tumors holds predictive value for tumor recurrence. Together, these data establish Gata3 as an important regulator of prostate cancer progression. |
