Cdh11 acts as a tumor suppressor in a murine retinoblastoma model by facilitating tumor cell death.
CDH11 gene copy number and expression are frequently lost in human retinoblastomas and in retinoblastomas arising in TAg-RB mice. To determine the effect of Cdh11 loss in tumorigenesis, we crossed Cdh11 null mice with TAg-RB mice. Loss of Cdh11 had no gross morphological effect on the developing retina of Cdh11 knockout mice, but led to larger retinal volumes in mice crossed with TAg-RB mice (p = 0.01). Mice null for Cdh11 presented with fewer TAg-positive cells at postnatal day 8 (PND8) (p = 0.01) and had fewer multifocal tumors at PND28 (p = 0.016), compared to mice with normal Cdh11 alleles. However, tumor growth was faster in Cdh11-null mice between PND8 and PND84 (p = 0.003). In tumors of Cdh11-null mice, cell death was decreased 5- to 10-fold (p<0.03 for all markers), while proliferation in vivo remained unaffected (p = 0.121). Activated caspase-3 was significantly decreased and beta-catenin expression increased in Cdh11 knockdown experiments in vitro. These data suggest that Cdh11 displays tumor suppressor properties in vivo and in vitro in murine retinoblastoma through promotion of cell death.
Marchong
Mellone N
MN
Campbell Family Institute for Cancer Research, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
Yurkowski
Christine
C
Ma
Clement
C
Spencer
Clarellen
C
Pajovic
Sanja
S
Gallie
Brenda L
BL
D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009154:Mutation; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; C086960:osteoblast cadherin