Download catenin

The MIN mouse:
(1.) Heterozygous for the highly penetrant ApcMin
allele.
(2.) Min/Min homozygotes die at gastrulation.
(3.) Mice develop numerous (50-200) adenomas in
the small intestine, and few (0-3) in the colon.
(4.) Death occurs around 5 months of age.
(5.) Tumor multiplicity modulated by genetic
background, drugs, and diet.
wnt
frizzled
dsh
E-cadherin  -catenin
P slimb
GSK3
 -catenin
conductin/axin
-catenin
APC
 -catenin
LEF/ TCF
 -catenin
LEF/ TCF
Target Genes
100X
GROUP
4 wks
10 wks
15 wks
5-FU (410 wks)
RTX (410 wks)
5-FU/RTX (410 wks)
TUMOR #
16  1 (N=25)
23  7 (N=9)
63  8 (N=7)
7  4 (N=13)
114  60 (N=7)
3  1 (N=12)
Untreated
Treated
(Tomudex 5mg/kg)
Folate-deficient diet
Does the genetic character of stromal
(i.e., bone marrow-derived) cells
determine response to
anti-neoplastic agents?
The role of the tumor stroma in conferring response
to TS inhibitors.
Marrow response
to drug ex vivo
Introduce
TS gene
Transplant
Tumor response
to drug therapy
eGFP Donor
MIN Recipient
Bone Marrow
Therapeutic
toxicity
MARROW
Normal
TS Overexpressing
THERAPY TUMOR # p-VALUE
-
32 ± 19
+
8±5
-
35 ± 22
+
19 ± 23
0.008
0.183