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

Paula Chakravarti; Matthew K Henry; Frederick W Quelle

doi:10.3892/ijo.26.2.509

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

Journal article

Peer reviewed

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

Paula Chakravarti, Matthew K Henry and Frederick W Quelle

International journal of oncology, Vol.26(2), pp.509-514

02/2005

DOI: 10.3892/ijo.26.2.509

PMID: 15645137

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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 gamma-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.

Phosphorylation

Cell Proliferation

Signal Transduction

Cell Survival

Humans

Gene Expression Regulation, Neoplastic

Morpholines - pharmacology

Neuregulin-1 - physiology

Phosphatidylinositol 3-Kinases - metabolism

DNA - metabolism

Blotting, Western

Prolactin - physiology

Breast Neoplasms - metabolism

Cell Cycle

Cell Line, Tumor

DNA Damage

Chromones - pharmacology

Growth Substances

Details

Title: Subtitle: Prolactin and heregulin override DNA damage-induced growth arrest and promote phosphatidylinositol-3 kinase-dependent proliferation in breast cancer cells
Creators: Paula Chakravarti - Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Matthew K Henry
Frederick W Quelle
Resource Type: Journal article
Publication Details: International journal of oncology, Vol.26(2), pp.509-514
Publisher: Greece
DOI: 10.3892/ijo.26.2.509
PMID: 15645137
ISSN: 1019-6439
eISSN: 1791-2423
Grant note: R01 CA79889 / NCI NIH HHS
Language: English
Date published: 02/2005
Academic Unit: Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040569202771

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