Role of K-ras oncogene in human pancreatic duct carcinogenesis.
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Word Count
21,000 words, Guess
Page Count
84 pages
Identifiers
- ISBN-100612913880
- ISBN-139780612913882
- Open LibraryOL19747119M
Description
Pancreatic cancer is a devastating disease. Mutations of K-ras gene occur early in the pancreatic ductal precursor lesions, accumulate with disease progression, and have been identified in over 90% of infiltrating pancreatic cancers. However, the pathogenic role of K-ras mutation in the conversion of normal pancreatic duct epithelial cells to tumorigenic cells remains unknown. Here, we demonstrate that the HPV-16E6E7 -immortalized human pancreatic ductal epithelial (HPDE6c7) cells transduced with mutated K-ras (G12V) formed tumors when implanted into SCID mice subcutaneously and orthotopically. Gene expression profiling using an oligonucleotide microarray platform indicates that the transcription of numerous genes was altered by K-ras oncogene transduction. The low tumorigenicity conferred by K-ras oncogene suggests a critical role for K-ras mutation in the early steps of human pancreatic ductal carcinogenesis. This established in vitro cell model can be further employed to dissect other genetic lesions associated with the pathogenesis of pancreatic cancers.
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