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Updated: Jul 16, 2026
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells
C M Perks1, E G Vernon, A H Rosendahl
1IGF & Metabolic Endocrinology Group, Department of Clinical Sciences at North Bristol, Southmead Hospital, University of Bristol, Bristol, UK. Claire.m.perks@bristol.ac.uk
Oncogene
|March 21, 2007
Summary
Insulin-like growth factor II (IGF-II) resistance in breast cancer cells involves PTEN induction. IGF-binding protein 2 (IGFBP-2) can suppress PTEN, impacting growth factor pathway therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor gene frequently mutated in cancers.
- PTEN counteracts growth factor signaling, notably insulin-like growth factor II (IGF-II), and its expression is regulated by IGF-II.
- IGF-binding proteins (IGFBPs) modulate IGF actions, and their role in PTEN regulation within cancer cells is under investigation.
Purpose of the Study:
- To investigate how IGF-binding proteins (IGFBPs) modulate IGF-II actions on MCF-7 breast cancer cells.
- To determine the specific role of IGFBP-2 in regulating PTEN expression and IGF-II responsiveness in breast cancer cells.
Main Methods:
- Utilized MCF-7 breast cancer cells and an IGF-II analog that does not bind IGFBPs.
- Employed specific antibodies to block IGFBP-2 and inhibitors to prevent IGF-IGFBP association.
- Assessed PTEN induction and cell responsiveness to IGF-II under various experimental conditions.
Main Results:
- MCF-7 cells showed resistance to high IGF-II doses due to PTEN induction.
- This resistance was abrogated when IGF-II could not bind IGFBPs or when IGFBP-2 was blocked.
- Free IGFBP-2 was found to suppress PTEN induction, restoring IGF-II responsiveness in specific conditions.
Conclusions:
- Breast cancer cells' unresponsiveness to high IGF-II is mediated by PTEN induction.
- IGFBP-2, particularly when not bound to IGF-II, can suppress PTEN.
- Elevated IGFBP-2 in tumors suggests potential therapeutic implications for targeting growth factor pathways.
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