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本帖最后由 细胞海洋 于 2013-4-26 22:58 编辑
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Since its discovery in the early 1990s the deleted in colorectal cancer2 @) R# C7 ]( c6 K4 i) V. B
(DCC) gene, located on chromosome 18q21, has been proposed as& n* V% b% W3 `4 a2 k) g/ l( i
a tumour suppressor gene as its loss is implicated in the majority of
+ F: f2 _; }; m6 A# Gadvanced colorectal and many other cancers; F7 k; h; D. ^7 _: P
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. DCC belongs to the1 G) c- p: B! Y4 B# Q
family of netrin 1 receptors, which function as dependence receptors, ]/ |: C; ^4 L( A* D* M3 A; L! U
as they control survival or apoptosis depending on ligand binding.
7 {- W/ C! X* t: T8 xHowever, the role of DCC as a tumour suppressor remains contro-versial because of the rarity of DCC-specific mutations and the pres-ence of other tumour suppressor genes in the same chromosomal
" U2 _( L1 \- S J0 q# r- Pregion. Here we show that in a mouse model of mammary carcinoma; I& h/ _! w! k0 ]- p# x
based on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour
3 Z- p/ i: D% a# Y( Fphenotype. Furthermore, we demonstrate that in cell cultures: W- v# t; q& c, a) S
derived from p53-deficient mouse mammary tumours DCC expres-sion controls netrin-1-dependent cell survival, providing a mech-anistic basis for the enhanced metastatic capacity of tumour cells
6 N8 N& V4 y& u5 E) qlacking DCC. Consistent with this idea, in vivo tumour-cell survival
3 b2 t! T3 |( n3 S" V( wis enhanced by DCC loss. Together, our data support the function of$ _) s: W6 J* b$ ?( M
DCC as a context-dependent tumour suppressor that limits survival
0 u m1 B6 D& ~& c. s9 Y+ bof disseminated tumour cells.9 A& c/ s6 ~# R. U8 C
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发表于 2013-4-25 20:29
