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本帖最后由 细胞海洋 于 2013-4-26 22:58 编辑 " Q+ D3 |# Z9 }) t' p
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Since its discovery in the early 1990s the deleted in colorectal cancer
, Y$ R; P, }: _4 z: v; J5 {(DCC) gene, located on chromosome 18q21, has been proposed as
; q2 d ?( ~, t0 aa tumour suppressor gene as its loss is implicated in the majority of
' O- R+ \- C# ?6 p6 Oadvanced colorectal and many other cancers& w/ O4 D& \- A% \
1
8 ^8 q9 J1 d1 s7 t. DCC belongs to the
! k' Y6 _7 y9 x& C" Y$ nfamily of netrin 1 receptors, which function as dependence receptors
u/ C7 O' p* c" ?3 Las they control survival or apoptosis depending on ligand binding. n& p, g, ~6 \2 y+ {
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
6 w6 \9 t3 }$ C7 N/ Lregion. Here we show that in a mouse model of mammary carcinoma
5 e7 ?: J% A% @" Q+ X- qbased on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour
, R1 J9 E9 N: P" ~8 s% k, lphenotype. Furthermore, we demonstrate that in cell cultures( [' q f, x6 N' Y: e
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 cells6 o1 w4 q1 }4 ?6 W+ V
lacking DCC. Consistent with this idea, in vivo tumour-cell survival; ]) |7 z/ c4 k; ]' p g" u5 b7 ?( H! K
is enhanced by DCC loss. Together, our data support the function of
; |! y$ n- e' y4 Z% jDCC as a context-dependent tumour suppressor that limits survival/ |8 i* h6 r1 ~% J" ]6 ]
of disseminated tumour cells.; {3 E8 E- Y$ s. h; P1 M3 e
& u0 G2 }& P' n1 h) m* l M[hide][/hide] |
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发表于 2013-4-25 20:29
