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About the Cover

Cover image

Cover image expansion

Upper: The cytokeratin 19 (K19) promoter was fused to K-ras-V12 (mutation of the K-ras oncogene at codon 12 with a change of Glycine to Valine) and targeted in a cell-type specific fashion to pancreatic ductal cells of transgenic mice. The resulting phenotype is that of pancreatic periductal lymphocytic infiltration (see Figure 2B of paper in this issue) and occasional pancreatic ductal hyperplasia (Cover Figure), both of which are not evident in age-matched wild type littermates. The pancreatic ductal hyperplasia corresponds to a human pancreatic intraepithelial lesion (PanIN). The advantage of this approach in the mouse is the recapitulation of the earliest stage of human pancreatic adenocarcinoma. In addition, mutant ras induces the expression of N-cadherin in transgenic mice but not age-matched wild-type littermates based upon gene array studies and confirmed by RNA and protein expression, which may have implications upon cell adhesion and motility in premalignant lesions of the pancreas. For more information, please see the article by Brembeck et al., on p. 2005 of this issue.

Lower: The photomicrograph shows a mutant Kras-induced mouse exocrine pancreatic lesion resembling noninvasive intraductal papillary-mucinous carcinomas that develop in humans. The lesion is separated from morphologically normal acini by a band of connective tissue. These and similar lesions develop in transgenic mice following acinar-cell targeting of a codon 12 mutant Kras, and they appear to arise via acinar-to-ductal metaplasia. Most lesions neither invade into adjacent pancreas nor metastasize, implicating Kras in early stages of lesion development but not progression. For more information, please see the article by Grippo et al., on p. 2016 of this issue.

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Cancer Research: 63 (9)
May 2003
Volume 63, Issue 9
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Issue Highlights

  • The Mutant K-ras Oncogene Causes Pancreatic Periductal Lymphocytic Infiltration and Gastric Mucous Neck Cell Hyperplasia in Transgenic Mice
  • Preinvasive Pancreatic Neoplasia of Ductal Phenotype Induced by Acinar Cell Targeting of Mutant Kras in Transgenic Mice
  • Obtustatin
  • Triple Analysis of the Cancer Epigenome
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Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

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