Differential display of expressed genes in pancreatic cancer cells.
Activating K-ras mutations occur in 80-95% of pancreatic cancers. The purpose of this study was to conduct an open, panoramic survey of gene expression, using K-ras status as the axis over which to sub-classify pancreatic cancers. Differential display was used to contrast mRNA purified from exponentially growing PANC-1 and Capan-2 cells (mutated K-ras) with Hs766T and BxPC-3 cells (wild-type). Differences were confirmed by Northern analysis. Twenty-five transcripts were differentially expressed by a factor of two or more. Four transcripts were over-expressed and twelve were under-expressed in the mutants relative to the wild-types. The transcripts most strikingly over-expressed by the mutant cell lines were MARCKS, DKFZp547C244, and RPLP2. The transcripts over-expressed by the wild-types were CEACAM6, cDNA AK026924, and myosin light chain-6. Profiling of gene expression with respect to K-ras mutation status may lead to new insights into pancreatic cancer pathogenesis, as well as to the identification of novel therapeutic targets.
Gardner-Thorpe
James
J
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. jgt@doctors.org.uk
Ito
Hiromichi
H
Ashley
Stanley W
SW
Whang
Edward E
EE
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D005260:Female; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D009154:Mutation; D018994:Myosin Light Chains / Q000235:genetics; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018994:Myosin Light Chains; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate