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BMP-2 is involved in the fetal and postnatal development of the mammary gland but has also been detected in breast cancer cells. To clarify the biological role of BMP-2 in breast cancer, we used the human breast cancer cell line MCF-7. Incubation with BMP-2 under serum-free conditions induced activation of the mitogen activated protein kinases (MAPKs) ERK1/2 and the basic helix-loop-helix transcription factors Id-1, proteins that can protect from apoptosis. Stably transfected MCF-7 cells overexpressing BMP-2 revealed significantly increased resistance to hypoxia-induced apoptosis compared to empty vector controls. Cytoplasmic BMP-2/4 protein expression was detected in carcinoma cells of 81 samples of invasive breast cancer in contrast to adjacent normal mammary epithelial cells. BMP-2/4 expression did not correlate with common prognostic parameters and was not associated with relapse-free or overall survival. We conclude that BMP-2/4 expression is reactivated in invasive breast cancer and part of an autocrine/paracrine mechanism rescuing malignant cells from hypoxic cell death via activation of the MAPK and Id-1 pathway.

Type

Journal article

Journal

Int j oncol

Publication Date

06/2005

Volume

26

Pages

1465 - 1470

Keywords

Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Bone Morphogenetic Proteins, Breast Neoplasms, Cell Death, Cell Hypoxia, Cell Line, Tumor, Female, Humans, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Prognosis, Transforming Growth Factor beta