Related Experiment Video

Updated: Aug 8, 2026

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

A genome-wide survey of RAS transformation targets

J Zuber1, O I Tchernitsa, B Hinzmann

  • 1[1] Laboratory of Molecular Tumour Pathology, Institute of Pathology, Charité, Humboldt-University D-10117, Berlin, Germany.

Nature Genetics
|February 2, 2000
PubMed

Insights

RAS gene mutations drive cancer by altering gene expression. This study identified numerous gene expression changes in HRAS-transformed cells, revealing potential cancer targets and pathways like RAF/MEK/ERK.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • RAS gene family mutations are crucial in multi-step tumorigenesis, especially in pancreatic, colon, lung, and myeloid cancers.
  • RAS proteins act as signal transduction switches, controlling gene expression and cellular processes like transformation and metastasis.
  • Oncogenic RAS proteins remain constitutively active, driving downstream signaling pathways.

Purpose of the Study:

  • To investigate differential gene expression profiles between normal and HRAS-transformed rat cells.
  • To identify novel and known genes regulated by RAS transformation.
  • To explore common and distinct targets of HRAS, KRAS, and NRAS, and identify RAF/MEK/ERK pathway targets.

Main Methods:

  • Utilized subtractive suppression hybridization (SSH), a PCR-based cDNA subtraction technique.
  • Analyzed over 1,200 subtracted cDNA fragments for differential gene expression.
  • Investigated gene expression changes in reverted cells treated with the MEK-specific inhibitor PD 98059.

Main Results:

  • Identified transcriptional stimulation or repression of 104 ESTs, 45 novel sequences, and 244 known genes in HRAS-transformed cells.
  • Discovered common and distinct gene expression targets for HRAS, KRAS, and NRAS transformation.
  • Identified 61 putative target genes regulated by the RAF/MEK/ERK pathway.

Conclusions:

  • RAS gene activation significantly alters cellular gene expression profiles.
  • The identified genes represent potential therapeutic targets for RAS-driven cancers.
  • The RAF/MEK/ERK pathway plays a significant role in mediating RAS-induced gene expression changes.

More Related Videos

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes08:32

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

Published on: May 23, 2025

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
The Ras Gene02:38

The 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...
Small GTPases - Ras and Rho01:24

Small 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:
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Ras Gene02:38

The 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...