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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 cancer5 j! V& L8 l* Y& _ ~9 R
(DCC) gene, located on chromosome 18q21, has been proposed as
: ~4 U7 T" e9 j7 P1 Ga tumour suppressor gene as its loss is implicated in the majority of7 r# A- w7 P. ^% c8 x+ k( O8 s
advanced colorectal and many other cancers$ }( ]9 Z; l9 ~) m9 I. T
1+ G+ k. }7 W$ ^
. DCC belongs to the
0 v" |+ ^5 Y0 n( a' B ]family of netrin 1 receptors, which function as dependence receptors! d4 Z0 _# p+ I+ {2 I5 J. \. G* c6 P
as they control survival or apoptosis depending on ligand binding.; h8 U# {! I3 U! g) e: A9 v: Q
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
) N" {% T8 Q" a' K. s8 q' b) b! Oregion. Here we show that in a mouse model of mammary carcinoma
5 s ?. l) A: g( {- {3 Y$ ibased on somatic inactivation of p53, additional loss of DCC pro-motes metastasis formation without affecting the primary tumour
+ A% a: I; F: ^5 z' x7 x/ ]- Y2 xphenotype. Furthermore, we demonstrate that in cell cultures
% f% M, `& S) Nderived 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; p( @2 p, K' |# Y5 e
lacking DCC. Consistent with this idea, in vivo tumour-cell survival& w' g1 M9 v' {/ b) K9 M- k! c
is enhanced by DCC loss. Together, our data support the function of
" b- {1 {+ o5 ?% R5 {; m3 GDCC as a context-dependent tumour suppressor that limits survival' |2 e h5 J/ s* T! H
of disseminated tumour cells.6 }4 X" m2 q u! s9 o) H! r; B# t
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发表于 2013-4-25 20:29
