Related Experiment Video

Updated: Aug 7, 2026

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

Early induction of ribonucleotide reductase gene expression by transforming growth factor beta 1 in malignant H-ras

R A Hurta1, S K Samuel, A H Greenberg

  • 1Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.

The Journal of Biological Chemistry
|December 15, 1991
PubMed

Insights

Transforming growth factor (TGF) beta 1 regulates ribonucleotide reductase gene expression in malignant cells, influencing DNA synthesis. This study reveals TGF-beta 1

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Transforming growth factor (TGF) beta 1 typically suppresses cell proliferation, but can stimulate tumor growth.
  • Loss of TGF-beta 1-mediated growth suppression is common in cellular transformation.
  • Ribonucleotide reductase is a key enzyme regulating DNA synthesis.

Purpose of the Study:

  • To investigate the link between TGF-beta 1 and ribonucleotide reductase gene expression during cellular transformation.
  • To explore the role of TGF-beta 1 in regulating DNA synthesis in malignant cells.
  • To elucidate the mechanism of autocrine stimulation by TGF-beta 1 in cancer.

Main Methods:

  • Analysis of ribonucleotide reductase M1 and M2 gene expression in radiation and T24-H-ras-transformed mouse 10T1/2 cell lines.
  • Evaluation of TGF-beta 1 induced alterations in M1 and M2 message and protein levels.
  • Transfection of T24-H-ras-transformed cells with a TGF-beta 1 expression plasmid under a metallothionein promoter.

Main Results:

  • Malignant cell lines showed early increases in ribonucleotide reductase M1 and/or M2 message and protein levels.
  • TGF-beta 1 induced changes in M1/M2 gene expression preceded detectable alterations in DNA synthesis rates.
  • Zinc-induced TGF-beta 1 expression in transfected cells led to rapid induction of M1 and M2 mRNA levels.

Conclusions:

  • TGF-beta 1 can elevate ribonucleotide reductase gene expression without altering the proportion of cells in S phase.
  • Early alterations in ribonucleotide reductase regulation may be crucial for TGF-beta 1-mediated autocrine stimulation of malignant cells.
  • The findings suggest a novel mechanism of cancer cell growth regulation involving TGF-beta 1 and ribonucleotide reductase.

More Related Videos

Inducible and Reversible Dominant-negative (DN) Protein Inhibition08:35

Inducible and Reversible Dominant-negative (DN) Protein Inhibition

Published on: January 7, 2019

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

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

Published on: October 27, 2020

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...
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...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
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:
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...