Expression and function of PIM kinases in osteosarcoma.
The provirus integrating site Moloney murine leukemia virus (PIM) family of serine/threonine protein kinases is composed of three members, PIM1, PIM2 and PIM3, which have been identified as oncoproteins in various malignancies. However, their role in osteosarcoma (OS) remains largely unknown. This study aimed to examine the expression patterns and the clinical significance of PIM kinases in human OS and their biological effects in human OS cell lines. Immunohistochemical staining was used to detect PIM kinases in archived pathologic material from 43 patients with primary OS; in addition, the effects of PIM knockdown and overexpression on the proliferation, migration and invasion of OS cell lines were determined. We observed that all three PIM kinases were frequently expressed in OS, but only PIM1 positive expression was associated with poorer prognosis regarding overall survival of OS patients. In addition, knockdown of PIM kinases notably inhibited OS cell proliferation, migration and invasiveness, whereas overexpression of PIM kinases resulted in increased OS cell growth and motility. This study suggests that PIM1 could be a valuable prognostic marker in patients with OS, and the biological functions of PIM kinase family in the osteosarcoma cell lines indicate that they could serve as potential therapeutic targets for OS.
Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Shuai
S
Mou
Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Guangbin
G
Wang
Department of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Ding
D
Ding
Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Dongdong
D
Yu
Department of Orthopaedics, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 11004, P.R. China.
Yi
Y
Pei
Department of Orthopaedics, Central Hospital of Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China.
Songling
S
Teng
Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Qin
Q
Fu
D000328:Adult; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim