Adenoviral-mediated gene transfer of ectodysplasin-A2 results in induction of apoptosis and cell-cycle arrest in osteosarcoma cell lines

被引:15
作者
Chang, B.
Punj, V.
Shindo, M.
Chaudhary, P. M.
机构
[1] Univ Pittsburgh, Hillman Canc Ctr, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA
[2] UT SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA
[3] Tottori Univ, Fac Med, Dept Dermatol, Tottori 680, Japan
关键词
ectodysplasin-A2; X-linked ectodermal dysplasia receptor; osteosarcoma; EDA-A2; XEDAR; apoptosis;
D O I
10.1038/sj.cgt.7701078
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The extremely poor prognosis of patients with metastatic osteosarcoma indicates the need for novel therapeutic approaches. Ectodysplasin-A2 (EDA-A2) is a recently isolated member of the tumor necrosis factor superfamily that binds to X-linked ectodermal dysplasia receptor (XEDAR). In this report, we have analyzed the biological activity of EDA-A2 against osteosarcoma-derived cell lines. We report that XEDAR is expressed in cell lines derived from osteosarcoma and adenoviral-mediated expression of EDA-A2 in these cells results in the induction of apoptosis via caspase activation and cell-cycle arrest in the G(0)/G(1) phase. Treatment with EDA-A2 also upregulates the expression of alkaline phosphatase, a marker of osteogenic differentiation, in a caspase-dependent fashion. Collectively, our results suggest that EDA-A2 may be a promising agent for the gene therapy of osteosarcoma.
引用
收藏
页码:927 / 933
页数:7
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