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Wild-Type Hras Suppresses the Earliest Stages of Tumorigenesis in a Genetically Engineered Mouse Model of Pancreatic Cancer.

Publication ,  Journal Article
Weyandt, JD; Lampson, BL; Tang, S; Mastrodomenico, M; Cardona, DM; Counter, CM
Published in: PLoS One
2015

Oncogenic, activating mutations in KRAS initiate pancreatic cancer. There are, however, two other Ras family members, Nras and Hras, which can be activated in the presence of oncogenic Kras. The role of these wild-type Ras proteins in cancer remains unclear, as their disruption has been shown to enhance or inhibit tumorigenesis depending upon the context. As pancreatic cancer is critically dependent upon Ras signaling, we tested and now report that loss of Hras increases tumor load and reduces survival in an oncogenic Kras-driven pancreatic adenocarcinoma mouse model. These effects were traced to the earliest stages of pancreatic cancer, suggesting that wild-type Hras may suppress tumor initiation. In normal cells, activated Ras can suppress proliferation through p53-dependent mechanisms. We find that the tumor suppressive effects of Hras are nullified in a homozygous mutant p53 background. As such, loss of wild-type Hras fosters the earliest stages of pancreatic cancer in a p53-dependent manner.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2015

Volume

10

Issue

10

Start / End Page

e0140253

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Signal Transduction
  • Proto-Oncogene Proteins p21(ras)
  • Pancreatic Neoplasms
  • Mutation
  • Mice, Transgenic
  • Mice
  • Humans
  • General Science & Technology
  • Cell Proliferation
 

Citation

APA
Chicago
ICMJE
MLA
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Weyandt, J. D., Lampson, B. L., Tang, S., Mastrodomenico, M., Cardona, D. M., & Counter, C. M. (2015). Wild-Type Hras Suppresses the Earliest Stages of Tumorigenesis in a Genetically Engineered Mouse Model of Pancreatic Cancer. PLoS One, 10(10), e0140253. https://doi.org/10.1371/journal.pone.0140253
Weyandt, Jamie D., Benjamin L. Lampson, Sherry Tang, Matthew Mastrodomenico, Diana M. Cardona, and Christopher M. Counter. “Wild-Type Hras Suppresses the Earliest Stages of Tumorigenesis in a Genetically Engineered Mouse Model of Pancreatic Cancer.PLoS One 10, no. 10 (2015): e0140253. https://doi.org/10.1371/journal.pone.0140253.
Weyandt JD, Lampson BL, Tang S, Mastrodomenico M, Cardona DM, Counter CM. Wild-Type Hras Suppresses the Earliest Stages of Tumorigenesis in a Genetically Engineered Mouse Model of Pancreatic Cancer. PLoS One. 2015;10(10):e0140253.
Weyandt, Jamie D., et al. “Wild-Type Hras Suppresses the Earliest Stages of Tumorigenesis in a Genetically Engineered Mouse Model of Pancreatic Cancer.PLoS One, vol. 10, no. 10, 2015, p. e0140253. Pubmed, doi:10.1371/journal.pone.0140253.
Weyandt JD, Lampson BL, Tang S, Mastrodomenico M, Cardona DM, Counter CM. Wild-Type Hras Suppresses the Earliest Stages of Tumorigenesis in a Genetically Engineered Mouse Model of Pancreatic Cancer. PLoS One. 2015;10(10):e0140253.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2015

Volume

10

Issue

10

Start / End Page

e0140253

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Signal Transduction
  • Proto-Oncogene Proteins p21(ras)
  • Pancreatic Neoplasms
  • Mutation
  • Mice, Transgenic
  • Mice
  • Humans
  • General Science & Technology
  • Cell Proliferation