|
- 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
! w1 ~, a1 T! [: J; C4 ?2 ~
. K# s* s) @2 U' |( k3 PSince its discovery in the early 1990s the deleted in colorectal cancer- @! |& u+ O. m2 L
(DCC) gene, located on chromosome 18q21, has been proposed as' C! r+ t4 \2 C- ]
a tumour suppressor gene as its loss is implicated in the majority of
# X4 ?& ^$ a1 D* c3 x) Xadvanced colorectal and many other cancers8 C, C) {; n' \& X3 d+ \' n
1
" y* V1 {" |& W# s6 X. DCC belongs to the' m: ?% P8 e y
family of netrin 1 receptors, which function as dependence receptors
$ @6 b& b; G! ras they control survival or apoptosis depending on ligand binding.
% [6 x# g% q7 t# n% {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 chromosomal5 X% J2 F* r1 Q
region. Here we show that in a mouse model of mammary carcinoma8 R3 M% U% y! E; y7 n2 M6 N/ _
based on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour
2 B% ]! c2 f: S/ tphenotype. Furthermore, we demonstrate that in cell cultures& n: ?8 S. y$ `& \6 e: k! y
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; J8 [. l2 a) U( w4 Y( G& I) d
lacking DCC. Consistent with this idea, in vivo tumour-cell survival
; \" ^4 H& f8 ^1 }3 r& h; E1 fis enhanced by DCC loss. Together, our data support the function of3 f# \; |% h( w4 c: R5 d
DCC as a context-dependent tumour suppressor that limits survival# x- b( J" ]2 t& w2 w$ k
of disseminated tumour cells.
, }2 W% a$ @( k' X: w; B7 n, u5 D
5 U3 }" ` F. z2 ~. w7 Q: Z: a, c1 d[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
