title: Increased levels of hypoxia-inducible factor-1α are associated with Bcl-xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma.
abstract: Hypoxia-inducible factor (HIF)-1α is a key nuclear transcription factor that regulates the cellular response to hypoxia, and is important for solid tumor growth and survival. However, the underlying role of HIF-1α in human chondrosarcoma has not been well characterized. This study aims to investigate the expression patterns of HIF-1α in chondrosarcoma, and its association with clinicopathologic features, Bcl-xL expression, apoptosis index (AI), and overall survival of patients with chondrosarcoma. Our results shown that the protein levels of HIF-1α were increased, and the mRNA and protein levels of Bcl-xL were also increased in SW1353 cells under hypoxic conditions. In eight patients with chondrosarcoma, increased expression of HIF-1α and Bcl-xL was detected in chondrosarcoma tissues compared with the paired adjacent normal tissues. Of 34 archival specimens of chondrosarcomas, 20 (58.8%) showed high HIF-1α protein expression as compared to benign cartilage tumors. Increased HIF-1α expression was correlated with a higher pathological grade and MSTS stage of chondrosarcoma. Moreover, HIF-1α expression was significantly associated with Bcl-xL expression and AI. More significantly, the survival rate of patients with HIF-1α high tumors was significantly lower than that of patients with HIF-1α low tumors. These findings suggest that increased HIF-1α levels mediated up-regulation of Bcl-xL play a prominent role in evasion of apoptosis and tumor progression, and can be predictive for the prognosis in human chondrosarcoma.
authors.affiliation: Department of Orthopaedic Surgery, Peking University Third Hospital, 49 North Garden Road, Beijing 100191, China.
authors.forename: Changbao
authors.initials: C
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Liang
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Liu
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001859:Bone Neoplasms / Q000737:chemistry / Q000473:pathology*; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D051020:bcl-X Protein / Q000032:analysis*
chemical_list: C494811:BCL2L1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051020:bcl-X Protein