873 The “Trojan Horse” Strategy: Selective Eradication of Cancer Cells by Adenovirus-Based Delivery of Cytotoxic Agents: An Alternative Method for Targeting Pancreatic (PC) and Colorectal Cancers (CRC)

G A A b st ra ct s have one truncated, non-functional copy of Apc and one wild-type copy. Apc is essential for constitutive cytosolic degradation of β-catenin and in the ApcMin/+ model somatic mutation inactivates the second copy of Apc, leading to tumorigenesis. In ApcMin/+Hsp70-/tumors, β-catenin mRNA was comparable to controls, but cytosolic protein was decreased while ubiquitination was increased. This suggests that β-catenin degradation is increased in ApcMin/+Hsp70-/tumors. Since β-catenin degradation requires Apc, we examined Apc expression in Hsp70-/versus Hsp70+/+ tumors. Tumors from ApcMin/+Hsp70+/+ mice had the expected loss of Apc expression, whereas tumors from ApcMin/+Hsp70-/mice were positive for Apc. Thus, Hsp70 is required for the loss of heterozygosity seen in the ApcMin/+ model of intestinal tumorigenesis. In conclusion, Hsp70 overexpression plays a key role in tumor initiation through promotion of gene editing and tumor proliferation through nuclear transport of β-catenin. Hence, Hsp70 presents an attractive target for tumor therapy and prevention in genetically predisposed individuals.