title: Downregulation of RSK2 influences the biological activities of human osteosarcoma cells through inactivating AKT/mTOR signaling pathways.
abstract: RSK2 (90 kDa ribosomal S6 kinase) is a downstream effector of the Ras/ERK (extracellular signal-regulated kinase) signaling pathway that has major functions in cell biological activities, including regulating nuclear signaling, cell cycle progression, cell proliferation, cell growth, protein synthesis, cell migration and cell survival, and is expressed in most types of human malignant tumors, including lung cancer, prostate and breast tumors, skin cancer and osteosarcomas (OS). RSK2 was found to be essential for osteosarcoma formation. To investigate whether RSK2 is expressed at high levels in human osteosarcome tissues and whether its expression is correlated with the aggressive biological behavior of osteosarcoma cell line (OCLs), we assessed the association between RSK2 expression and OS cell progression, as well as the effects of RSK2 inhibition on the biological activities of osteosarcoma cells. We performed immunohistochemistry to analyze the expression of RSK2 in specimens from 30 humans with osteosarcoma, and 15 normal tissues. RSK2 gene expression levels in 30 specimens with osteosarcoma were significantly higher than those of normal tissues. We performed RNA interference on three OCLs to evaluate cell apoptosis, cell growth, cell proliferation, cell motility, chemosensitivity and oncogenicity. After transfection with RSK2 shRNA, increased cell apoptosis, cell growth inhibition, cell cycle progression, weaker cell proliferation, cell migration and weaker tumor formation were observed in all OCLs. These results suggested that RSK2 expression may mediate the biological activities of OS cells and RSK2 may be an effective therapeutic target for the treatment of osteosarcomas. The AKT/mTOR, MAPK/ERK/c-Fos and Bcl2/Bax pathways were analysed to clarify the mechanisms involved.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Quanhe
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Clinical Laboratory, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liangbo
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Neimenggu Medical University, Huhehaote, Neimeng 010030, P.R. China.
authors.forename: Daqi
authors.initials: D
authors.lastname: Xin
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3