Liver, Pancreas, and Biliary TractSuppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo☆,☆☆
Section snippets
Materials
The following were purchased: fetal bovine serum (FBS), Dulbecco's modified Eagle medium (DMEM), trypsin ethylenediaminetetraacetic acid solution, and penicillin-streptomycin (Irvine Scientific, Santa Ana, CA); Geneticin (G418; Gibco BRL, Grand Island, NY); GeneScreen membranes (New England Nuclear, Boston, MA); restriction enzymes and random-primed labeling kit (Boehringer-Mannheim, Indianapolis, IN); [α-32P]deoxycytidine triphosphate (3000 Ci/mmol) and enhanced chemiluminescence (ECL)
Expression of wild-type and transfected FGFR
Northern blot analysis revealed the major FGFR-1 messenger RNA transcript (~4.4 kb) in control PANC-1 cells as well as in transfected cells (Figure 2A).
Discussion
The PANC-1 cell line is a well-characterized human pancreatic cancer cell line that expresses FGFR-1 and produces bFGF and KGF.23, 24 In addition, PANC-1 cells express high levels of EGFR42 and harbor mutations in the K-ras oncogene9, 34 and the p53 tumor-suppressor gene.9, 35 Overexpression of FGFR-1 and EGFR and mutations in K-ras and p53 are observed in a majority of human pancreatic cancers.4, 6, 9, 10, 11, 12, 26, 42, 43, 44, 45, 46 Therefore, PANC-1 cells reflect a molecular pattern that
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2015, Developmental CellCitation Excerpt :Support for this notion comes from early in vitro and in vivo evidence suggesting that injury or oncogenic transformation can drive acinar cells toward a ductal phenotype (Arias and Bendayan, 1993; De Lisle and Logsdon, 1990; Grippo and Sandgren, 2000; Hall and Lemoine, 1992; Vila et al., 1994; Yuan et al., 1997). Acinar transdifferentiation into ductal metaplasia can lead to premalignant lesions as shown by EGFR, TGF-α, SV40 large T antigen, or KrasG12D expression in pancreatic acinar cells (Bockman and Merlino, 1992; Grippo et al., 2003; Ornitz et al., 1987; Sandgren et al., 1990; Tuveson et al., 2006; Wagner et al., 2001, 1998). Using Nestin-Cre animals, Murray Korc’s group provided further support for the notion that acinar cells, or their progenitors, can give rise to neoplastic cells with ductal features (Carrière et al., 2007).
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Address requests for reprints to: Murray Korc, M.D., Division of Endocrinology, Diabetes and Metabolism, Medical Sciences I, C240, University of California, Irvine, Irvine, California 92697. Fax: (714) 824-1035.
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Supported by U.S. Public Health Service grant CA-40162 from the National Institutes of Health (to M.K.). Dr. Wagner was the recipient of a postdoctoral fellowship award from the Swiss National Science Foundation (Bern, Switzerland).