Related Experiment Video
Updated: Aug 2, 2026
12:40
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Differences in in vitro invasive capacity induced by differences in Ki-Ras protein mutations
1Kuwait University, Faculty of Medicine, Department of Pathology (Molecular Pathology Laboratory), P.O. Box 24923, Safat, Kuwait 13110. fahd@al-mulla.org
The Journal of Pathology
|December 18, 2001
Summary
The valine-12 mutation in Ki-Ras proteins enhances cell invasion more than the aspartate-12 mutation, offering new insights into aggressive tumor behavior and guiding future research on Ras mutations.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ras proteins, including Ki-Ras, are key regulators of cell signaling pathways.
- Specific mutations in Ki-ras codon-12, such as valine-12, are linked to more aggressive lung and colorectal cancers compared to aspartate-12 mutations.
Purpose of the Study:
- To investigate if different Ki-ras codon-12 mutants (valine-12 vs. aspartate-12) exhibit distinct in vitro biological behaviors.
- To determine if these in vitro differences correlate with observed in vivo tumor aggressiveness.
Main Methods:
- Rat-1 fibroblasts were transfected with wild-type Ki-ras, valine-12 mutant Ki-ras, or aspartate-12 mutant Ki-ras genes.
- Cells were assessed for in vitro invasion using Matrigel, cellular transformation, and vascular endothelial growth factor (VEGF) production.
Main Results:
- Both valine-12 and aspartate-12 Ki-ras mutants induced significant cell transformation and VEGF production, unlike wild-type Ki-ras.
- Valine-12 mutants showed a significantly greater capacity for Matrigel invasion compared to aspartate-12 mutants and wild-type Ki-ras.
Conclusions:
- This study demonstrates a significant difference in Matrigel invasion in vitro between valine-12 and aspartate-12 Ki-ras mutants.
- These findings support previous data on differential in vivo effects of Ras mutations and highlight the need to investigate the underlying mechanisms of these biological variations.
More Related Videos
Related Concept Videos
01:16In-vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity: