Increased levels of hypoxia-inducible factor-1α are associated with Bcl-xL expression, tumor apoptosis, and clinical outcome in chondrosarcoma.
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.
Chen
Changbao
C
Department of Orthopaedic Surgery, Peking University Third Hospital, 49 North Garden Road, Beijing 100191, China.
Zhou
Hua
H
Wei
Feng
F
Jiang
Liang
L
Liu
Xiaoguang
X
Liu
Zhongjun
Z
Ma
Qingjun
Q
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*
C494811:BCL2L1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051020:bcl-X Protein