Increasing evidence suggests that the three homologous members of steroid receptor co-activator (SRC) family (SRC-1, SRC-2, and SRC-3) play key roles in enhancing cell proliferation in various human cancers, such as breast, prostate, and hepatocellular carcinoma. However, the function of SRC-3 in osteosarcoma remains largely unexplored. In the current study, we found that SRC-3, but not SRC-1 and SRC-2, was dramatically up-regulated in human osteosarcoma tissues, compared with adjacent normal tissues. To explore the functions of SRC-3 in osteosarcoma, in vitro studies were performed in MG63 and U2OS cells. SRC-3 overexpression promoted osteosarcoma cell proliferation, whereas knockdown of SRC-3 inhibits its proliferation. In support of these findings, we further demonstrated that SRC-3 up-regulated FoxM1 expression through co-activation of C/EBPγ. Together our results show that SRC-3 drives osteosarcoma progression and imply it as a therapeutic target to abrogate osteosarcoma.
Osteosarcoma Transcription SRC-3 FoxM1 C/EBPγ
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This work was partially supported by National Natural Science Foundation of China (81271984), Research Fund for the Doctoral Program of Higher Education of China (20122307120036), Natural Science Foundation for Returnees of Heilongjiang Province of China (LC2012C11), Research Fund for Returnees of Education Department of Heilongjiang Province of China (1253HQ003), Research Fund of the First Affiliated Hospital of Harbin Medical University(2013LX01).
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