Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cancer+Res 2014 ; 74 (17): 4875-87 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
TRIM29 suppresses TWIST1 and invasive breast cancer behavior #MMPMID24950909
Ai L; Kim WJ; Alpay M; Tang M; Pardo CE; Hatakeyama S; May WS; Kladde MP; Heldermon CD; Siegel EM; Brown KD
Cancer Res 2014[Sep]; 74 (17): 4875-87 PMID24950909show ga
TRIM29 (ATDC) exhibits a contextual function in cancer, but appears to exert a tumor suppressor role in breast cancer. Here we show that TRIM29 is often silenced in primary breast tumors and cultured tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial-mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival (RFS), increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT.
free
free
free
Cancer+Res 2014 ; 74 (17): 4875-87
