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Published on: December 1, 2015

Insulin-like growth factor-II regulates PTEN expression in the mammary gland

Roger A Moorehead1, Carlo V Hojilla, Ian De Belle

  • 1Ontario Cancer Institute/University Health Network, University of Toronto, Toronto, Ontario M5G 2M9, Canada.

The Journal of Biological Chemistry
|October 1, 2003
PubMed

Insights

Insulin-like growth factor-II (IGF-II) boosts tumor suppressor PTEN expression in the mammary gland. This discovery reveals a new feedback loop in the PI3K pathway, impacting cell growth and cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The tumor suppressor PTEN is frequently altered in cancers, including breast cancer, and is crucial for regulating cell survival and proliferation via the PI3K/Akt pathway.
  • Known regulators of PTEN expression are limited, highlighting a gap in understanding how its activity is controlled.

Purpose of the Study:

  • To investigate the role of insulin-like growth factor-II (IGF-II) in regulating PTEN expression within the mammary gland.
  • To elucidate the molecular mechanisms by which IGF-II influences PTEN and downstream signaling pathways.

Main Methods:

  • IGF-II was administered to mouse mammary glands, and PTEN expression levels were analyzed.
  • Transgenic mice with altered IGF-II expression were used to study long-term effects on mammary tissue.
  • PTEN promoter activity and the involvement of the gene egr-1 were assessed.

Main Results:

  • IGF-II injection significantly increased PTEN expression in the mouse mammary gland.
  • Elevated IGF-II levels in transgenic mice led to increased PTEN protein, decreased Akt phosphorylation, and reduced epithelial proliferation.
  • IGF-II stimulation enhanced PTEN promoter activity, mediated by the immediate early gene egr-1.

Conclusions:

  • IGF-II acts as a novel regulator of PTEN expression in the mammary gland.
  • A negative feedback loop is identified where IGF-II induces PTEN to modulate its own physiological effects within the PI3K pathway.
  • This finding provides new insights into cancer development and potential therapeutic strategies targeting the PI3K pathway.

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