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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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0 e& t( \5 E/ T V$ [- ySince its discovery in the early 1990s the deleted in colorectal cancer
/ O/ \' x( u- E(DCC) gene, located on chromosome 18q21, has been proposed as
/ R, \5 V0 h7 X) o9 Ga tumour suppressor gene as its loss is implicated in the majority of7 d0 Z; H+ Q& }( u
advanced colorectal and many other cancers
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: _* O& U8 V1 C8 p% h2 H. DCC belongs to the+ k4 U$ X8 k |7 P& Y% _
family of netrin 1 receptors, which function as dependence receptors
r) }+ ?2 Z# P; {- I6 V# i' s+ F$ tas they control survival or apoptosis depending on ligand binding.4 ?9 T9 ^) V* v9 M1 _
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) z6 r9 B. s3 S% i' G
region. Here we show that in a mouse model of mammary carcinoma
+ u( U0 T2 I2 g' F$ z4 G+ g' ?based on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour
Q1 \: ]- G+ V5 sphenotype. Furthermore, we demonstrate that in cell cultures
# t$ U8 o1 i. sderived 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
( M% q3 v' P M8 ^8 Hlacking DCC. Consistent with this idea, in vivo tumour-cell survival3 M7 D+ Z* h8 L
is enhanced by DCC loss. Together, our data support the function of) A& C% g& ^" `- z6 \# K& z
DCC as a context-dependent tumour suppressor that limits survival; b* Y t8 n# S4 ]
of disseminated tumour cells.+ \5 ]" Q; B7 k4 Y
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发表于 2013-4-25 20:29
