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本帖最后由 细胞海洋 于 2013-4-26 22:58 编辑 " x' S- z7 ^5 `" N
. x% K8 ?/ M+ ]6 i! @7 |Since its discovery in the early 1990s the deleted in colorectal cancer
$ z* z4 k4 O+ b* w j(DCC) gene, located on chromosome 18q21, has been proposed as7 u4 C- X4 z5 Z0 p( h
a tumour suppressor gene as its loss is implicated in the majority of
: v; P8 j/ R; T/ K; Madvanced colorectal and many other cancers
! r. c3 S l! ]* K) K- ]1
9 W) h$ D: y. S8 c- x: |. D. DCC belongs to the' z& l# z6 x9 l6 d4 n0 G& Q
family of netrin 1 receptors, which function as dependence receptors9 S; q2 ^. i) Z9 Q8 W$ }# `- [
as they control survival or apoptosis depending on ligand binding.; T$ X" @4 S+ F2 {0 j7 m; X( ?
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
( P w G, q" \4 Yregion. Here we show that in a mouse model of mammary carcinoma- v5 u3 g/ _% T* N, n4 L& _
based on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour
' `' t' o# e% o8 i, E8 Vphenotype. Furthermore, we demonstrate that in cell cultures
3 A7 u+ o# \5 S% yderived 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
: T. {; m$ W: A {. f$ s) Llacking DCC. Consistent with this idea, in vivo tumour-cell survival( B- _3 {9 q* I: A' A" v, J
is enhanced by DCC loss. Together, our data support the function of
0 ~, h9 W6 Y! D# C' ]DCC as a context-dependent tumour suppressor that limits survival* X3 }( j4 ~2 g) i+ s0 ]( k; P" o
of disseminated tumour cells.' u2 z7 b6 D0 h) s1 _
V8 D/ X. K/ s3 ?8 Y- E1 p j[hide][/hide] |
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发表于 2013-4-25 20:29
