Histological Complexities of Pancreatic Lesions from Transgenic Mouse Models Are Consistent with Biological and Morphological Heterogeneity of Human Pancreatic Cancer

Although pancreatic cancer is the fourth leading cause of cancer death, it has received much less attention compared to other malignancies. There are several transgenic animal models available for studies of pancreatic carcinogenesis, but most of them do not recapitulate, histologically, human pancreatic cancer. Here we review some detailed molecular complexity of human pancreatic cancer and their reflection in histomorphological complexities of pancreatic lesions developed in various transgenic mouse models with a special concern for studying the effects of chemotherapeutic and chemopreventive agents. These studies usually require a large number of animals that are at the same age and gender and should be either homozygote or heterozygote but not a mixture of both. Only single-transgene models can meet these special requirements, but many currently available models require a mouse to simultaneously bear several transgene alleles. Thus it is imperative to identify new gene promoters or enhancers that are specific for the ductal cells of the pancreas and are highly active in vivo so as to establish new single-transgene models that yield pancreatic ductal adenocarcinomas for chemotherapeutic and chemopreventive studies.