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Activation of Raf-1 in Human Pancreatic Adenocarcinoma
Journal article   Peer reviewed

Activation of Raf-1 in Human Pancreatic Adenocarcinoma

David H. Berger, Lori A. Jardines, Hong Chang, Bruce Ruggeri and Hsihui Chang
The Journal of surgical research, v 69(1)
Apr 1997
DOI: https://doi.org/10.1006/jsre.1997.5022
PMID: 9202670
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Point mutations in the Ras oncogene cause Ras to remain in its active GTP-bound state sending signals downstream continuously. Since 75 to 90% of all human pancreatic ductal adenocarcinomas harbor activating mutations at codon 12 of the K-ras oncogene it was our belief that Raf-1–;MEK–;MAPK will be activated in the majority of human pancreatic cancers. The aim of this study was to confirm activation of Raf-1 in K-ras mutant human pancreatic cancer. Additionally, we sought to determine if Raf-1 activation differed in K-ras mutant and nonmutant pancreatic cancer. Futhermore, we were interested in determining if Raf-1 activation in pancreatic cancer led to subsequent activation of downstream effectors such as MAP kinase. The presence of mutations in codon 12 of the K-ras oncogene in 14 human pancreatic adenocarcinoma cell lines was determined by use of mutant allele-specific PCR restriction fragment length polymorphism analysis. Raf-1 expression of quiescent cells was determined by immunoblotting using a rabbit anti-human polyclonal antibody and enhanced chemiluminescence. MAP kinase activity was determined by measuring the incorporation of phosphate into Myelin Basic Protein. Seven cell lines were noted to have mutations in codon 12 of K-ras while seven cell lines did not. There was no difference in expression of the 74 kDa-activated form of Raf-1 in K-ras mutant vs K-ras nonmutant cell lines. However, there was a significant increase in MAP kinase activity in the nonmutant cell lines compared to the cell lines with Ras mutations (P= 0.026). We conclude that Raf-1 is expressed in its active form in human pancreatic cancer regardless of K-ras status. However, signaling downstream of Raf-1 differs in cell lines with K-ras mutations compared to those cell lines without K-ras mutations.

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Web of Science research areas
Surgery
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