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Updated: Jul 16, 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-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
PubMed

Insights

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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