Transducin (ß)-like 1 X-linked receptor 1 promotes proliferation and tumorigenicity in human breast cancer via activation of beta-catenin signaling (Breast Cancer Research)

IntroductionTransducin (?)-like 1 X-linked receptor 1(TBLR1) is an F-box-like and WD repeat-containing protein which functions as a switch in transcriptional activation, However, the clinical significance and biological role of TBLR1 in breast cancer remains largely unknown. Methods: Western blotting, immunocytochemistry and real-time PCR were used to evaluate TBLR1 expression in normal breast epithelial cells and breast cancer cell lines, clinical tissue samples and adjacent nontumor tissues, and in 214 paraffin-embedded specimens. Statistical analyses were used to test for the prognostic and diagnostic associations. The biological role of TBLR1 -induced proliferation and tumorigenicity in breast cancer cells was explored in vitro and in vivo. The effect of TBLR1 on the expression of cyclin D1 and ?-catenin signaling was examined by Western blotting, luciferase reporter assay and by several immunoprecipitation techniques. Results: TBLR1 was significantly upregulated in breast cancer cells and tissues compared to normal control samples. Immunohistochemical analysis revealed high expression of TBLR1 in 113 of 214 (52.8%) paraffin-embedded archival breast cancer. The overall expression level of TBLR1 was significantly correlated with clinical stage (P