title: Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11.
abstract: Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment.
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.|Department of Endocrinology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie Fang Avenue, Wuhan, 430022, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.|Center for Computational and Integrative Biology (CCIB), Massachusetts General Hospital, Boston, Massachusetts 02139USA.
authors.forename: Slim
authors.initials: S
authors.lastname: Sassi
authors.affiliation: Center for Computational and Integrative Biology (CCIB), Massachusetts General Hospital, Boston, Massachusetts 02139USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Halvorsen
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.|Department of Orthopaedic Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie Fang Avenue, Wuhan, 430022, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.
authors.forename: Jacson
authors.initials: J
authors.lastname: Shen
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Hematology and Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Cote
authors.affiliation: Division of Hematology and Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.affiliation: Division of Hematology and Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: David
authors.initials: D
authors.lastname: Harmon
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Mankin
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Hornicek
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114USA.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D018844:Cyclin-Dependent Kinases / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D012516:Osteosarcoma / Q000473:pathology*; D011379:Prognosis; D011944:Receptors, Androgen / Q000032:analysis*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; C584437:CDK19 protein, human; D018844:Cyclin-Dependent Kinases