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 β-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

Cdh11 Acts as a Tumor Suppressor in a Murine Retinoblastoma Model by Facilitating Tumor Cell Death

Retinoblastoma, a rare childhood cancer of the retina, is characterized by loss of both alleles of the RB1 gene. However, additional mutational events are required for malignancy. CGH studies described common chromosomal changes indicating potential oncogenes and tumor suppressor genes. Previous work in the lab implicated Cadherin-11 (Cdh11) as a tumor suppressor after analysis in human retinoblastomas and in the simian virus 40 large T-antigen induced murine retinoblastoma model (TAg-RB) showed loss of Cdh11 expression. TAg-RB mice crossed with Cdh11-/- mice, revealed faster growing tumors in mice null for Cdh11. This thesis focused on defining the tumor suppressor role of Cdh11 in retinoblastoma progression. The results showed in vitro and in vivo evidence that Cdh11 was promoting apoptosis and not suppressing proliferation. We also observed an increase in invasion markers upon the loss of Cdh11. We conclude that Cdh11 acts as a tumor suppressor in retinoblastoma, through promotion of apoptosis.MAS

Abundance and species diversity hotspots of tracked marine predators across the North American Arctic

International audienceAim: Climate change is altering marine ecosystems worldwide and is most pronounced in the Arctic. Economic development is increasing leading to more disturbances and pressures on Arctic wildlife. Identifying areas that support higher levels of predator abundance and biodiversity is important for the implementation of targeted conservation measures across the Arctic.Location: Primarily Canadian Arctic marine waters but also parts of the United States, Greenland and Russia.Methods: We compiled the largest data setof existing telemetry data for marine predators in the North American Arctic consisting of 1,283 individuals from 21 species. Data were arranged into four species groups: (a) cetaceans and pinnipeds, (b) polar bears Ursus maritimus (c) seabirds, and (d) fishes to address the following objectives: (a) to identify abundance hotspots for each species group in the summer–autumn and winter–spring; (b) to identify species diversity hotspots across all species groups and extent of overlap with exclusive economic zones; and (c) to perform a gap analysis that assesses amount of overlap between species diversity hotspots with existing protected areas.Results: Abundance and species diversity hotpots during summer–autumn and winter–spring were identified in Baffin Bay, Davis Strait, Hudson Bay, Hudson Strait, Amundsen Gulf, and the Beaufort, Chukchi and Bering seas both within and across species groups. Abundance and species diversity hotpots occurred within the conti -nental slope in summer–autumn and offshore in areas of moving pack ice in winter–spring. Gap analysis revealed that the current level of conservation protection that overlaps species diversity hotspots is low covering only 5% (77,498 km2) in summer–autumn and 7% (83,202 km2) in winter–spring.Main conclusions: We identified several areas of potential importance for Arctic marine predators that could provide policymakers with a starting point for conservation measures given the multitude of threats facing the Arctic. These results are relevant to multilevel and multinational governance to protect this vulnerable ecosystem in our rapidly changing world