BRIT1 Regulates p53 Stability and Functions as a Tumor Suppressor in Breast Cancer
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant la stabilité de la protéine p53, le gène BRIT1, situé sur la région chromosomique 8p23.1, joue un rôle de suppresseur de tumeurs dans les cancers du sein
In humans, gene encoding the BRIT1 protein is located on chromosome 8p23.1, a region implicated in the development of several malignancies, including breast cancer. Previous studies by our group and others suggested that BRIT1 might function as a novel tumor suppressor. Thus, identifying the molecular mechanisms that underlie BRIT1’s tumor suppressive function is important to understand cancer etiology and to identify effective therapeutic strategies for BRIT1-deficient tumors. We thus investigated the role of BRIT1 as a tumor suppressor in breast cancer by using genetic approaches. We discovered that BRIT1 functions as a posttranscriptional regulator of p53 expression. BRIT1 regulates p53 protein stability through blocking murine double minute 2 (MDM2)-mediated p53 ubiquitination. To fully demonstrate the role of BRIT1 as a tumor suppressor, we depleted BRIT1 in normal breast epithelial cells. We found that knockdown of BRIT1 caused the oncogenic transformation of normal mammary epithelial cells. Furthermore, ectopic expression of BRIT1 effectively suppressed breast cancer cell proliferation and colony formation in vitro and tumor growth in vivo. Taken together, our study provides new insights into the biological functions of BRIT1 as a tumor suppressor in human breast cancer.
http://carcin.oxfordjournals.org/content/early/2013/06/01/carcin.bgt190.abstract