To assess whether mir-17~92 deletion impairs progression to carcinoma, we accelerated the KC model by including conditional loss of one copy of Trp53 (LSL-KrasG12D, Trp53flox/wt, Ptf1a-Cre and mir-17~92flox/flox, LSL-KrasG12D, Trp53flox/wt, Ptf1a-Cre; hereafter “KPC” and “17KPC” mice). We observed that KPC and 17KPC mice display similar overall survival and tumor size (Figure 4A, 4B). Rates of liver metastasis are also equivalent between groups (Supplementary Figure 5A, 5B). The carcinomas identified in mice of both genotypes displayed a mixture of glandular and undifferentiated histology; no difference in the relative frequencies of the histologic types was identified between the two groups (Supplementary Figure 5C–5E). Histological evidence of invasion was also equally prevalent in both groups, and variously involved the stomach/duodenum, liver, colon, and spleen (Supplementary Figure 5F–5J). The histopathology findings are summarized in Supplementary Table 1. Additionally, tumors across both groups exhibited similar rates of proliferation and apoptosis as demonstrated by Ki67 and cleaved caspase 3 (CC3) staining (Supplementary Figure 6). Moreover, KPC and 17KPC tumors display equivalent MEK/ERK pathway activation as measured by immunostaining for phosphorylated ERK (Supplementary Figure 7A, 7B). Further, cell lines derived from KPC and 17KPC tumors display similar levels of ERK phosphorylation and similar levels of DUSP7 and DUSP10 expression (Supplementary Figure 7C, 7D). Together, these findings suggest that heterozygous deletion of Trp53 compensates for the loss of mir-17~92 and promotes disease progression in mir-17~92 deficient animals.