Related Experiment Video
Updated: Jun 13, 2026
09:08
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
ErbB2 induces Notch1 activity and function in breast cancer cells
Jaime Lindsay1, Xuanmao Jiao, Toshiyuki Sakamaki
1Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Clinical and Translational Science
|May 7, 2010
Summary
ErbB2 oncogene in breast cancer activates Notch1 signaling. This pathway involves cyclin D1, which amplifies Notch1 activity by inhibiting Numb, promoting tumor growth.
Area of Science:
- Molecular oncology
- Cell signaling pathways
Background:
- ErbB2 (Her2/neu) oncogene overexpression is common in human breast cancers.
- Cyclin D1 is a key regulator of cell cycle progression and a downstream target of ErbB2.
- The Notch signaling pathway plays a critical role in cell proliferation and differentiation.
Purpose of the Study:
- To investigate the relationship between ErbB2 and Notch1 signaling in breast cancer.
- To elucidate the role of cyclin D1 in mediating ErbB2-induced Notch1 activity.
- To identify the molecular mechanisms by which cyclin D1 influences Notch1 activity.
Main Methods:
- Utilized mammary epithelial cells and Foxed Notch (Notch(fl/fl)) mice models.
- Employed genetic deletion and small interfering RNA (siRNA) to manipulate gene expression.
- Assessed DNA synthesis, contact-independent growth, and mammosphere formation.
- Measured Notch1 activity and Numb expression levels.
Main Results:
- ErbB2 was demonstrated to induce Notch1 signaling pathway activity.
- Notch1 was essential for ErbB2-induced DNA synthesis, contact-independent growth, and mammosphere formation.
- Cyclin D1 was identified as a downstream target of Notch1, and it amplifies Notch1 activity by inhibiting Numb.
Conclusions:
- ErbB2 promotes breast cancer growth by inducing Notch1 activity.
- Cyclin D1 acts downstream of Notch1, amplifying its activity by repressing Numb.
- This study reveals a novel pathway where ErbB2 induces Notch1 activity via cyclin D1 induction.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:20The 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,...
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,...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.