Dataset Information

DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma.

ABSTRACT: Deleted in breast cancer 1 (DBC1/CCAR2) is a protein of interest because of its diverse roles in tumorigenesis and its possible role as an androgen receptor (AR) co-activator. However, there are limited studies on the role of DBC1 in osteosarcoma. Therefore, we investigated the role of DBC1 and AR and their relationship in osteosarcoma. Immunohistochemical expression of DBC1 and AR was significantly associated with higher clinical stage and higher histologic grade, and predicted shorter survival. Especially, DBC1 expression was an independent prognostic indicator of overall survival (p?=?0.005) and relapse-free survival (p?=?0.004) by multivariate analysis. In osteosarcoma cell lines, U2OS and SaOS2, the knock down of DBC1 and AR with siRNA significantly reduced cellular proliferation and inhibited proliferation-related signaling. In addition, the knock down of DBC1 and AR decreased the invasion activity and inhibited invasion-related signaling of osteosarcoma cells. Interestingly, DBC1 affects the stabilization of AR protein via a mechanism involving the ubiquitination of AR. Proteosome-mediated degradation and poly-ubiquitination of AR were increased with the knock-down of DBC1. In conclusion, this study has shown that DBC1 is involved in the stabilization of AR protein and DBC1-AR pathways might be involved in the progression of osteosarcoma.

SUBMITTER: Wagle S

PROVIDER: S-EPMC4642542 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma.

Wagle Sajeev S Park See-Hyoung SH Kim Kyoung Min KM Moon Young Jae YJ Bae Jun Sang JS Kwon Keun Sang KS Park Ho Sung HS Lee Ho H Moon Woo Sung WS Kim Jung Ryul JR Jang Kyu Yun KY

Scientific reports 20150807

Deleted in breast cancer 1 (DBC1/CCAR2) is a protein of interest because of its diverse roles in tumorigenesis and its possible role as an androgen receptor (AR) co-activator. However, there are limited studies on the role of DBC1 in osteosarcoma. Therefore, we investigated the role of DBC1 and AR and their relationship in osteosarcoma. Immunohistochemical expression of DBC1 and AR was significantly associated with higher clinical stage and higher histologic grade, and predicted shorter survival ...[more]

PMID: 26249023

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Project description:BACKGROUND:FAM83H was initially identified as a protein essential for dental enamel formation. Recent reports have shown that FAM83H is also involved in the progression of human cancers in conjunction with tumor-associated molecules, such as MYC and ?-catenin. However, the role of FAM83H in sarcoma has not yet been investigated. METHODS:The expression and roles of FAM83H and ?-catenin were evaluated in human osteosarcomas from 34 patients and osteosarcoma cells. RESULTS:The expression of nuclear FAM83H, cytoplasmic FAM83H, and ?-catenin were significantly associated with each other and significantly associated with shorter survival of osteosarcoma patients by univariate analysis. In multivariate analysis, cytoplasmic expression of FAM83H was an independent indicator of shorter survival of osteosarcoma patients (overall survival; P?<? 0.001, relapse-free survival; P?<? 0.001). In U2OS, MG63, and KHOS/NP osteosarcoma cells, the knock-down of FAM83H decreased proliferation and invasion activity and overexpression of FAM83H increased proliferation and invasion activity. In KHOS/NP cells, knock-down of FAM83H significantly inhibited, and overexpression of FAM83H significantly increased in vivo growth of cells. In addition, the knock-down of FAM83H decreased protein expression of ?-catenin, active ?-catenin, cyclin D1, vimentin, and snail. Overexpression of FAM83H increased protein expression of ?-catenin, active ?-catenin, cyclin D1, vimentin, and snail. However, the expression of ?-catenin mRNA was not significantly altered with knock-down or overexpression of FAM83H. In addition, FAM83H and ?-catenin shown to directly interact via immunoprecipitation and nuclear and cytoplasmic localization of ?-catenin was decreased with knock-down of FAM83H. Moreover, the ubiquitination and proteasomal degradation of ?-catenin was increased with knock-down of FAM83H. CONCLUSIONS:This study suggests that FAM83H is involved in the progression of osteosarcomas via a mechanism involving the stabilization of ?-catenin and the promotion of proliferation and invasiveness of osteosarcomas.

Dataset Information

DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma.

Publications

DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma.

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