Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells

  • Authors:
    • Paula Chakravarti
    • Matthew K. Henry
    • Frederick W. Quelle
  • View Affiliations

  • Published online on: February 1, 2005     https://doi.org/10.3892/ijo.26.2.509
  • Pages: 509-514
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Abstract

Heregulin (HRG), a ligand of ErbB receptor tyrosine kinases, is a potent mitogenic factor for breast cancer cells. Prolactin (PRL) has also been reported to regulate proliferation in breast cancer cells through its receptor, a member of the type I cytokine receptor family. Cytokine receptors are potent mitogens in hematopoietic cells, where they also override DNA damage-induced growth arrest checkpoints through activation of a phosphatidylinositol-3 kinase (PI3K) signaling pathway. In this study, we assessed the effect of γ-irradiation on the mitogenic activity of HRG and PRL in breast cancer cells. HRG and PRL enhanced the proliferation of non-irradiated breast cancer cell lines in association with their ability to activate PI3K signaling pathways. Both growth factors also overrode irradiation-induced growth arrest in T47D cells, which resulted in decreased viability after irradiation. An inhibitor of PI3K, LY294002, abrogated growth factor-induced proliferation and the activity of cell cycle-dependent kinases in non-irradiated and irradiated cells. Thus, growth factors acting through distinct receptor families share a similar PI3K-dependent ability to promote proliferation and override DNA damage-induced growth arrest in breast cancer cells. These observations also suggest that selective activation of PI3K-dependent signaling can enhance radiosensitivity in breast cancer cells.

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February 2005
Volume 26 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chakravarti P, Henry MK and Quelle FW: Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells. Int J Oncol 26: 509-514, 2005
APA
Chakravarti, P., Henry, M.K., & Quelle, F.W. (2005). Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells. International Journal of Oncology, 26, 509-514. https://doi.org/10.3892/ijo.26.2.509
MLA
Chakravarti, P., Henry, M. K., Quelle, F. W."Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells". International Journal of Oncology 26.2 (2005): 509-514.
Chicago
Chakravarti, P., Henry, M. K., Quelle, F. W."Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells". International Journal of Oncology 26, no. 2 (2005): 509-514. https://doi.org/10.3892/ijo.26.2.509