P53 induces angiogenesis-restricted dormancy in a mouse fibrosarcoma

被引:39
作者
Holmgren, L [1 ]
Jackson, G
Arbiser, J
机构
[1] Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden
[2] Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA
关键词
angiogenesis; dormancy; neoplasia;
D O I
10.1038/sj.onc.1201993
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The p53 tumor-suppressor gene is inactivated in over 50% of all human cancers, In normal cells, p53 induces growth arrest and apoptosis in response to DNA damage. We show that p53 acts as potent tumor-suppressor gene independent of its well-documented effects on tumor-cell proliferation and apoptosis. p53 activates target genes in a murine fibrosarcoma cell-line but does not affect tumor cell-cycle progression or survival. Exogenous expression of wt-p53 does, however, block the angiogenic potential of the tumor cells resulting in formation of dormant tumors in vivo. These data provide evidence that: (1) p53 acts as a tumor suppressor gene independent of its anti-proliferative effects; (2) By inhibiting angiogenesis p53 can indirectly induce apoptosis in vivo but not in vitro; (3) p53-gene therapy which alters a tumors angiogenic potential, can revert tumors to a dormant phenotype.
引用
收藏
页码:819 / 824
页数:6
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