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Publication : Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN.

First Author  Siveke JT Year  2007
Journal  Cancer Cell Volume  12
Issue  3 Pages  266-79
PubMed ID  17785207 Mgi Jnum  J:124969
Mgi Id  MGI:3723003 Doi  10.1016/j.ccr.2007.08.002
Citation  Siveke JT, et al. (2007) Concomitant Pancreatic Activation of Kras(G12D) and Tgfa Results in Cystic Papillary Neoplasms Reminiscent of Human IPMN. Cancer Cell 12(3):266-79
abstractText  Growth factors have been implicated in pancreatic carcinogenesis. In this study we analyzed the effect of Tgfa overexpression in addition to mutant Kras(G12D) by crossing Elastase-Tgfa mice with p48(+/Cre);Kras(+/LSL-G12D) mice. We show that concomitant expression of TGFalpha and Kras(G12D) accelerates the progression of mPanIN lesions to metastatic pancreatic cancer and leads to the development of cystic papillary lesions resembling human intraductal papillary mucinous neoplasms (IPMN). Microarray data in mice revealed an IPMN signature and IPMNs expressed MUC1 and MUC5AC but not MUC2, similar to human pancreatobiliary IPMNs. Invasive ductal adenocarcinoma developed from PanINs and IPMNs, suggesting precursor lines for both lesion types in this model. In conclusion, Egfr signaling in synergy with oncogenic Kras may be a prerequisite for IPMN development and progression to pancreatic cancer.
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