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本帖最后由 细胞海洋 于 2013-4-26 22:58 编辑
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Since its discovery in the early 1990s the deleted in colorectal cancer# ^: q, m3 w) H6 @* [
(DCC) gene, located on chromosome 18q21, has been proposed as/ t1 U9 W/ ^, w2 c. o6 e/ q
a tumour suppressor gene as its loss is implicated in the majority of
: d6 v1 F% w2 f h. x1 Dadvanced colorectal and many other cancers' n* t w0 o6 r# I4 J3 y9 T8 e
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. DCC belongs to the
/ i- [0 }/ S1 Z8 B+ K5 m. y: j. Dfamily of netrin 1 receptors, which function as dependence receptors
1 T3 I" K7 Q# [4 Sas they control survival or apoptosis depending on ligand binding.) \+ x) M# o& L; Z; [
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! }# z: ]6 \) m+ @- { y
region. Here we show that in a mouse model of mammary carcinoma
9 J N! c+ U" w& f' c. lbased on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour" W6 K' s& K: H0 d
phenotype. Furthermore, we demonstrate that in cell cultures1 M G' q/ P- f. 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 cells8 {7 T' r6 z) w9 Y8 A* R- o b0 N
lacking DCC. Consistent with this idea, in vivo tumour-cell survival4 d* L Y. Q& o) |9 M
is enhanced by DCC loss. Together, our data support the function of- {) F4 Q9 D7 P' D* q }3 L" ~5 G6 V, ?
DCC as a context-dependent tumour suppressor that limits survival
( O# S* v( r2 Q6 U! N$ uof disseminated tumour cells.- Q) ?: u* [/ m
- I A! k: J8 _. B& p: l9 k[hide][/hide] |
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发表于 2013-4-25 20:29
