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Phosphatidylinositol 3-kinase mediates heregulin-induced growth inhibition in human epithelial cells

A W Hamburger1, J Y Yoo

  • 1University of Maryland Cancer Center, Department of Pathology, Baltimore 21201, USA.

Anticancer Research
|May 1, 1997
PubMed

Insights

Heregulin beta 1 (HRG) differentially affects human mammary epithelial cell growth by activating phosphatidylinositol 3-kinase (PI-3K). Both growth inhibition and stimulation by HRG are mediated through PI-3K activation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Phosphatidylinositol 3-kinase (PI-3K) activation is crucial for heregulin (HRG)-induced mitogenesis in human breast epithelial cells.
  • The precise role of PI3K activation in HRG-mediated growth inhibition remains unclear.

Purpose of the Study:

  • To investigate the effects of heregulin beta 1 (HRG) on the growth and PI3K activation in a nonneoplastic human mammary epithelial cell line (184B5).

Main Methods:

  • Treatment of 184B5 cells with varying concentrations of HRG.
  • Assessment of cell growth via [3H] thymidine incorporation.
  • Measurement of erbB3 tyrosine phosphorylation and PI3K association with erbB3.
  • Utilizing wortmannin, a PI3K inhibitor, to evaluate pathway involvement.

Main Results:

  • Low HRG concentrations stimulated 184B5 cell growth threefold; high concentrations inhibited growth by 50%.
  • HRG consistently increased erbB3 tyrosine phosphorylation and PI3K-erbB3 association across all tested concentrations.
  • Wortmannin treatment reversed both the stimulatory and inhibitory effects of HRG on DNA synthesis.

Conclusions:

  • Both the growth-inhibitory and growth-stimulatory effects of HRG in nonneoplastic human mammary epithelial cells are mediated by phosphatidylinositol 3-kinase (PI-3K) activation.
  • This study elucidates a dual role for PI3K signaling in HRG-induced cellular responses within the mammary epithelium.

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