|
- 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
& @5 y9 g( H% f- [- W2 Y9 y1 ~; v/ P5 [' K
Since its discovery in the early 1990s the deleted in colorectal cancer
! ?& l3 l4 g1 y0 V- K* r' R(DCC) gene, located on chromosome 18q21, has been proposed as
6 v7 o% {9 k5 v. d* U. V3 wa tumour suppressor gene as its loss is implicated in the majority of3 m) D: J) z- c8 d: Z
advanced colorectal and many other cancers
. n8 g0 Z$ N4 e7 d+ Q2 C1& l; w( L+ ]% f7 _# G
. DCC belongs to the
* M) q8 L& C! Pfamily of netrin 1 receptors, which function as dependence receptors# k! S) ~, K) q! J$ ^7 @* X7 f
as they control survival or apoptosis depending on ligand binding.
2 C+ ]6 e+ c+ K5 N( [ H DHowever, 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
- e) k `5 ^: I* R1 l. o" kregion. Here we show that in a mouse model of mammary carcinoma \. X& R9 ~3 g% _2 v# J, d
based on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour4 q* C0 `. S# A4 A/ n
phenotype. Furthermore, we demonstrate that in cell cultures
3 i8 f, o% R: j. u- Q/ Lderived 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
% ^1 g" D' n0 I9 jlacking DCC. Consistent with this idea, in vivo tumour-cell survival3 u. e$ v/ Z7 {* e
is enhanced by DCC loss. Together, our data support the function of6 F3 X5 w3 ^/ m
DCC as a context-dependent tumour suppressor that limits survival3 V, Z+ y2 H2 h J' e
of disseminated tumour cells.
( s' o( Z5 X- |0 W$ k4 Y
+ L- G) y, b- _[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
