Ras-Driven Transformation of Human Nestin-Positive Pancreatic Epithelial Cells

Paul M. Campbell, Kwang M. Lee, Michel M Ouellette, Hong Jin Kim, Angela L. Groehler, Vladimir Khazak, Channing J. Der

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Mutational activation of the K-Ras oncogene is well established as a key genetic step in the development and growth of pancreatic adenocarcinomas. However, the means by which aberrant Ras signaling promotes uncontrolled pancreatic tumor cell growth remains to be fully elucidated. The recent use of primary human cells to study Ras-mediated oncogenesis provides important model cell systems to dissect this signaling biology. This chapter describes the establishment and characterization of telomerase-immortalized human pancreatic duct-derived cells to study mechanisms of Ras growth transformation. An important strength of this model system is the ability of mutationally activated K-Ras to cause potent growth transformation in vitro and in vivo. We have utilized this cell system to evaluate the antitumor activity of small molecule inhibitors of the Raf-MEK-ERK mitogen-activated protein kinase cascade. This model will be useful for genetic and pharmacologic dissection of the contribution of downstream effector signaling in Ras-dependent growth transformation.

Original languageEnglish (US)
Pages (from-to)451-465
Number of pages15
JournalMethods in Enzymology
Volume439
DOIs
StatePublished - 2008

Fingerprint

Nestin
Epithelial Cells
Growth
Dissection
Telomerase
Mitogen-Activated Protein Kinase Kinases
Cell growth
Mitogen-Activated Protein Kinases
ras Genes
Ducts
Pancreatic Ducts
Tumors
Growth and Development
Chemical activation
Cells
Carcinogenesis
Adenocarcinoma
Molecules
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Campbell, P. M., Lee, K. M., Ouellette, M. M., Kim, H. J., Groehler, A. L., Khazak, V., & Der, C. J. (2008). Ras-Driven Transformation of Human Nestin-Positive Pancreatic Epithelial Cells. Methods in Enzymology, 439, 451-465. https://doi.org/10.1016/S0076-6879(07)00431-4

Ras-Driven Transformation of Human Nestin-Positive Pancreatic Epithelial Cells. / Campbell, Paul M.; Lee, Kwang M.; Ouellette, Michel M; Kim, Hong Jin; Groehler, Angela L.; Khazak, Vladimir; Der, Channing J.

In: Methods in Enzymology, Vol. 439, 2008, p. 451-465.

Research output: Contribution to journalArticle

Campbell, Paul M. ; Lee, Kwang M. ; Ouellette, Michel M ; Kim, Hong Jin ; Groehler, Angela L. ; Khazak, Vladimir ; Der, Channing J. / Ras-Driven Transformation of Human Nestin-Positive Pancreatic Epithelial Cells. In: Methods in Enzymology. 2008 ; Vol. 439. pp. 451-465.
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