|
- 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 ; n8 I. h/ J" w [6 Y
% C0 W5 g2 ]" e h# F+ C8 @! o
Since its discovery in the early 1990s the deleted in colorectal cancer2 V0 z9 Y; k+ a$ J7 P
(DCC) gene, located on chromosome 18q21, has been proposed as
- `& R0 c) U/ W2 ?. Va tumour suppressor gene as its loss is implicated in the majority of
2 P. t: Z( |: o5 j+ {advanced colorectal and many other cancers
( W# [; U6 d- b1 @; f1 s0 ^1
! D% y/ g7 k7 n {) L& N/ R$ g. DCC belongs to the) H& m2 m) s4 a, M2 r
family of netrin 1 receptors, which function as dependence receptors
1 h( w9 N# e5 G7 sas they control survival or apoptosis depending on ligand binding.
. @, e: w/ ~$ |3 j/ S8 tHowever, 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
/ [7 ~% u, d- n& d1 ~$ Tregion. Here we show that in a mouse model of mammary carcinoma$ o. O/ H8 O* _
based on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour
! k$ R" ^$ J$ e, m! Y/ Nphenotype. Furthermore, we demonstrate that in cell cultures' j; O% `3 ~2 C. Z
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" T# q/ H& @& g
lacking DCC. Consistent with this idea, in vivo tumour-cell survival5 e* ^7 t: C5 K0 s- W4 w
is enhanced by DCC loss. Together, our data support the function of0 @ p* I3 S# w; X$ h
DCC as a context-dependent tumour suppressor that limits survival' t8 Q5 y# o5 I# P# N
of disseminated tumour cells., x2 O) y. f' C6 d( t2 l
" k J% e1 u0 w& X
[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
