Liao J D, Adsay N V, Khannani F, Grignon D, Thakur A, Sarkar F H
Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
Histol Histopathol. 2007 Jun;22(6):661-76. doi: 10.14670/HH-22.661.
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.
尽管胰腺癌是癌症死亡的第四大主要原因，但与其他恶性肿瘤相比，它受到的关注要少得多。有几种转基因动物模型可用于胰腺癌发生的研究，但其中大多数在组织学上并不能重现人类胰腺癌。在此，我们回顾人类胰腺癌的一些详细分子复杂性，以及它们在各种转基因小鼠模型中发生的胰腺病变的组织形态学复杂性中的反映，特别关注化疗和化学预防剂的作用研究。这些研究通常需要大量年龄和性别相同的动物，且应为纯合子或杂合子，而不是两者的混合。只有单转基因模型能满足这些特殊要求，但目前许多可用模型要求小鼠同时携带多个转基因等位基因。因此，必须鉴定出对胰腺导管细胞特异且在体内高度活跃的新基因启动子或增强子，以便建立能产生胰腺导管腺癌用于化疗和化学预防研究的新单转基因模型。
