title: BRIT1 regulates p53 stability and functions as a tumor suppressor in breast cancer.
abstract: In humans, the gene encoding the BRCA1 C terminus-repeat inhibitor of human telomerase expression 1 (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 post-transcriptional regulator of p53 expression. BRIT1 regulates p53 protein stability through blocking murine double minute 2-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.
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, The University of Huazhong Science & Technology, Wuhan, Hubei Province 430022, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Edward
authors.initials: E
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Dai
authors.forename: Ruozhen
authors.initials: R
authors.lastname: Hu
authors.forename: Yulong
authors.initials: Y
authors.lastname: Liang
authors.forename: Kaiyi
authors.initials: K
authors.lastname: Li
authors.forename: Guobin
authors.initials: G
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Peng
authors.forename: Shiaw-Yih
authors.initials: SY
authors.lastname: Lin
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D005260:Female; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051736:Proto-Oncogene Proteins c-mdm2