Related Experiment Video

Updated: Jun 30, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Transformation by oncogenic Ras expands the early genomic response to transforming growth factor beta in intestinal

Carl E Allen1, Jianguo Du, Bo Jiang

  • 1Center for Cell and Developmental Biology, The Research Institute at Nationwide Children's Hospital and the Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43205, USA.

Neoplasia (New York, N.Y.)
|September 25, 2008
PubMed

Insights

Transforming growth factor beta (TGFbeta) promotes tumors in resistant epithelial cells. Oncogenic Ras expands TGFbeta

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Transforming growth factor beta (TGFbeta) acts as a tumor suppressor in normal epithelial cells.
  • However, in resistant cells, TGFbeta can paradoxically promote tumor growth.
  • Understanding TGFbeta's role in resistant cells is crucial for cancer research.

Purpose of the Study:

  • To investigate early, genome-wide TGFbeta responses in intestinal epithelial cells resistant to TGFbeta's growth inhibitory effects.
  • To compare TGFbeta-regulated gene expression in normal versus oncogenic Ras-transformed cells.
  • To identify specific genes and pathways involved in TGFbeta-mediated tumor promotion in resistant cells.

Main Methods:

  • Microarray analysis was performed on sensitive (RIE-1) and resistant (RIE-Ras(12V)) rat intestinal epithelial cells.
  • Cells were treated with TGFbeta1, and gene expression changes were analyzed.
  • Key gene regulations were confirmed using Northern analysis.

Main Results:

  • TGFbeta1 treatment induced significant gene expression changes in both cell types.
  • Resistant RIE-Ras(12V) cells showed a substantially expanded transcriptional response to TGFbeta1 compared to RIE-1 cells (42 upregulated vs. 8 upregulated).
  • 37 unique, Ras-dependent TGFbeta1 genomic targets were identified, including connective tissue growth factor and vascular endothelial growth factor.

Conclusions:

  • Loss of sensitivity to TGFbeta growth inhibition does not abolish TGFbeta signaling; it expands the early transcriptional response.
  • Oncogenic Ras in intestinal epithelial cells significantly broadens the cellular response to TGFbeta.
  • Upregulated genes in Ras-transformed cells may contribute to tumor promotion characteristics.

More Related Videos

In Vitro Evaluation of Oncogenic Transformation in Human Mammary Epithelial Cells09:44

In Vitro Evaluation of Oncogenic Transformation in Human Mammary Epithelial Cells

Published on: September 24, 2020

Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Related Concept Videos

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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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:
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...
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...