Related Experiment Video

Updated: Sep 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

IGF-binding protein-3-induced growth inhibition and apoptosis do not require cell surface binding and nuclear

Alison J Butt1, Kristie A Fraley, Sue M Firth

  • 1Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. abutt@med.usyd.edu.au

Endocrinology
|June 20, 2002
PubMed

Insights

Insulin-like growth factor-binding protein-3 (IGFBP-3) inhibits human breast cancer cell growth and induces apoptosis through multiple pathways. Even without cell surface binding or nuclear translocation, IGFBP-3 effectively halts cell cycle progression and triggers programmed cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Insulin-like growth factor-binding protein-3 (IGFBP-3) exhibits antiproliferative and proapoptotic effects on human breast cancer cells.
  • The precise mechanisms underlying IGFBP-3's actions, including its potential cell surface receptor interactions and nuclear translocation involving RXRalpha, are not fully elucidated.

Purpose of the Study:

  • To investigate the distinct pathways through which IGFBP-3 influences human breast cancer cell growth and apoptosis.
  • To determine if IGFBP-3 can exert its growth-inhibitory and proapoptotic effects independently of cell surface binding and nuclear translocation.

Main Methods:

  • Utilized a mutant form of IGFBP-3 with impaired cell surface binding and nuclear translocation capabilities.
  • Assessed the effects of the mutant IGFBP-3 on human breast cancer cell proliferation, cell cycle progression (G1 arrest), and apoptosis.
  • Analyzed the modulation of Bcl-2 family members in response to IGFBP-3 treatment.

Main Results:

  • The mutant IGFBP-3, despite reduced cell surface association and lack of nuclear entry, retained significant growth inhibitory properties.
  • This mutant form effectively induced a G1 cell cycle arrest in human breast cancer cells.
  • Apoptosis was induced by the mutant IGFBP-3 through the modulation of Bcl-2 family proteins.

Conclusions:

  • IGFBP-3 mediates its growth-inhibitory and proapoptotic effects on human breast cancer cells via multiple, distinct pathways.
  • Cell surface binding and nuclear translocation are not essential for all of IGFBP-3's tumor-suppressive functions.
  • These findings suggest that targeting IGFBP-3 or its downstream effectors could be a viable strategy for breast cancer therapy.

More Related Videos

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Spheroid Assay to Measure TGF-β-induced Invasion09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

Related Concept Videos

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...
Mitogens and the Cell Cycle02:38

Mitogens 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...
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...