Comparison of ras-responsive gene enhancers in pancreatic tumor cells that express either wild-type or mutant K-ras

Phillip J. Wilder, Harini Chakravarthy, Michael A Hollingsworth, A Angie Rizzino

Research output: Contribution to journalArticle

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Abstract

There is a pressing need for new therapies to treat pancreatic cancer. In principle, this could be achieved by taking advantage of signaling pathways that are active in tumor, but not normal, cells. The work described in this study set out to determine whether the activities of three enhancers, which have been reported to be highly responsive to activated ras, differ in pancreatic tumor cells that express wild-type versus constitutively active mutant forms of K-ras. Surprisingly, the three enhancers are active in four different pancreatic tumor cell lines that express either normal K-ras gene or mutant K-ras. Moreover, reducing the concentration of serum in the growth medium from 10% to 0.5% had relatively little effect on the strength of any of the enhancers, although it drastically affected cell growth. Importantly, our studies also indicate that MEK is active in pancreatic tumor cells that possess wild-type as well as mutant K-ras, even when cultured in medium that severely limits cell growth. These findings support the hypothesis that the Ras/Raf/Mek/Erk pathway may be constitutively active even in pancreatic tumor cells that express wild-type K-ras.

Original languageEnglish (US)
Pages (from-to)706-711
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume381
Issue number4
DOIs
StatePublished - Apr 17 2009

Fingerprint

ras Genes
Tumors
Genes
Cells
Cell growth
Neoplasms
Growth
Mitogen-Activated Protein Kinase Kinases
Tumor Cell Line
Pancreatic Neoplasms
Serum

Keywords

  • Enhancer activity
  • K-ras
  • MEK
  • Pancreatic cancer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Comparison of ras-responsive gene enhancers in pancreatic tumor cells that express either wild-type or mutant K-ras. / Wilder, Phillip J.; Chakravarthy, Harini; Hollingsworth, Michael A; Rizzino, A Angie.

In: Biochemical and Biophysical Research Communications, Vol. 381, No. 4, 17.04.2009, p. 706-711.

Research output: Contribution to journalArticle

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