Frequently rearranged in advanced T‑cell lymphomas‑1 demonstrates oncogenic properties in prostate cancer.
Prostate cancer is the fifth most common cause of cancer‑associated mortality for males worldwide. Although dysregulation of the β‑catenin/T‑cell factor (TCF) pathway has been previously reported in prostate cancer, the mechanisms underlying this process remain unknown. Frequently rearranged in advanced T‑cell lymphomas‑1 (FRAT1) functions as a positive regulator of the β‑catenin/TCF signaling pathway. However, to the best of our knowledge, the molecular association between FRAT1 and the β‑catenin/TCF pathway in prostate cancer has not been investigated. In the present study, FRAT1 expression was analyzed in normal prostate tissues and prostate adenocarcinoma samples using publicly available databases, a commercial tissue microarray and immunohistochemistry techniques. In addition, FRAT1 expression levels were altered by overexpression or RNA interference‑mediated depletion in prostate cancer cells. The effects of FRAT1 expression on tumor growth were determined using cell growth curves in vitro and xenografts in nude mice in vivo. The effects of FRAT1 on β‑catenin/TCF activity were measured using the TOPFLASH reporter assay. FRAT1 was expressed exclusively in the nuclei of normal prostate basal cells, and nuclear FRAT1 was detected in 68% (40/59) of prostate adenocarcinoma samples. In addition, FRAT1 activated the TCF luciferase reporter gene promoter in prostate cancer cells, and was observed to promote the growth of prostate cancer cells in vitro. Furthermore, FRAT1 expression was sufficient to transform NIH3T3 mouse embryonic fibroblast cells and lead to tumor formation in vivo. These results suggest that FRAT1 demonstrates oncogenic properties in prostate cancer, potentially by suppressing the inhibitory effect of nuclear glycogen synthase 3β against β‑catenin/TCF activity, thus activating the Wnt/β‑catenin signaling pathway and promoting cell growth.
Department of Urology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China.
Wei
W
Zhang
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Hua
H
Xiong
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Yanmei
Y
Zou
Department of Pathology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Sanpeng
S
Xu
Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P.R. China.
Lanping
L
Quan
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Xianglin
X
Yuan
Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P.R. China.
Ningzhi
N
Xu
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
Yihua
Y
Wang
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C491819:FRAT1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D051176:beta Catenin