|
- 积分
- 22
- 威望
- 22
- 包包
- 146
|
本帖最后由 细胞海洋 于 2013-4-26 22:58 编辑 # d# R( Z. s! f- z* V8 t! {
& K; D% q. _5 p3 v
Since its discovery in the early 1990s the deleted in colorectal cancer
! o2 l3 [* I) B(DCC) gene, located on chromosome 18q21, has been proposed as/ C& U4 J- k; G9 s8 P1 h
a tumour suppressor gene as its loss is implicated in the majority of
' d2 e- q6 V$ c( ~) b1 k- [advanced colorectal and many other cancers, ?5 _" m" K" ?4 Q
1
/ ]7 h: |6 W! [. x @. DCC belongs to the
/ h4 k3 X0 z, l3 F( v9 Z8 hfamily of netrin 1 receptors, which function as dependence receptors! ~, N6 O5 U' f# N+ w
as they control survival or apoptosis depending on ligand binding.' s) X' u. A1 M0 D& m5 [( |
However, 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
+ c/ s/ w! ^- i; d! E6 Fregion. Here we show that in a mouse model of mammary carcinoma
6 N' P0 l! A G0 P3 T. d+ Tbased on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour8 E! D( Q# y! z4 B3 B" G
phenotype. Furthermore, we demonstrate that in cell cultures8 n# ~" p* H, l; r# z/ d$ F
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 cells1 v0 x/ t; @! j; a2 ^
lacking DCC. Consistent with this idea, in vivo tumour-cell survival9 F# G5 q3 e# T4 C& ~6 w
is enhanced by DCC loss. Together, our data support the function of( I" Q, m7 ^* j0 D
DCC as a context-dependent tumour suppressor that limits survival
5 y2 \7 u/ h0 X/ Q, Iof disseminated tumour cells.$ V. b% g4 |% j, ~9 f4 o
* Z7 u9 x# u5 s- u' T[hide][/hide] |
附件: 你需要登录才可以下载或查看附件。没有帐号？注册
|
发表于 2013-4-25 20:29
