Control of prostate cell growth: BMP antagonizes androgen mitogenic activity with incorporation of MAPK signals in Smad1.
Alterations in the signaling pathways of bone morphogenetic proteins (BMPs) and activation of the ERK/MAP kinase (MAPK) pathway by growth factors have been implicated in the development and progression of prostate cancer. Smad1 acts as a substrate for MAPKs and also performs a central role in transmitting signals from BMPs. ... We found that BMPs/Smad1 signaling inhibits the growth of androgen-sensitive prostate cancer cells. Upon the incorporation of ERK/MAPK signals at its linker region, Smad1 physically interacts with androgen-activated androgen receptor (AR) and suppresses its functions. BMPs induce the function of Smad1 as an AR transcriptional corepressor. We demonstrated in vivo that Smad1 signaling is low in androgen-regulated growth of prostate cancer, is activated after castration, and also is decreased in hormone-independent tumors. The activation status of ERK/MAPK parallels Smad1 in the progression of prostate cancer; thus, our findings indicate a molecular basis for the integration of signals of MAPK and Smad1 in the progression and androgen regulation of prostate cancer.
Mesh Terms:
Adenocarcinoma, Androgens, Animals, Bone Morphogenetic Proteins, Cell Proliferation, Cells, Cultured, Humans, Male, Mice, Mitogen-Activated Protein Kinases, Models, Biological, Prostate, Prostatic Neoplasms, Receptors, Androgen, Signal Transduction, Smad1 Protein, Xenograft Model Antitumor Assays
Adenocarcinoma, Androgens, Animals, Bone Morphogenetic Proteins, Cell Proliferation, Cells, Cultured, Humans, Male, Mice, Mitogen-Activated Protein Kinases, Models, Biological, Prostate, Prostatic Neoplasms, Receptors, Androgen, Signal Transduction, Smad1 Protein, Xenograft Model Antitumor Assays
EMBO J.
Date: Jan. 24, 2007
PubMed ID: 17183365
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