Deletion of the BMP receptor BMPR1a impairs mammary tumor formation and metastasis.

Pickup MW, Hover LD, Guo Y, Gorska AE, Chytil A, Novitskiy SV, Moses HL, Owens P
Oncotarget. 2015 6 (26): 22890-904

PMID: 26274893 · PMCID: PMC4673207 · DOI:10.18632/oncotarget.4413

Bone Morphogenetic Proteins (BMPs) are secreted cytokines/growth factors belonging to the Transforming Growth Factor β (TGFβ) family. BMP ligands have been shown to be overexpressed in human breast cancers. Normal and cancerous breast tissue display active BMP signaling as indicated by phosphorylated Smads 1, 5 and 9. We combined mice expressing the MMTV.PyMT oncogene with mice having conditional knockout (cKO) of BMP receptor type 1a (BMPR1a) using whey acidic protein (WAP)-Cre and found this deletion resulted in delayed tumor onset and significantly extended survival. Immunofluorescence staining revealed that cKO tumors co-expressed Keratin 5 and mesenchymal cell markers such as Vimentin. This indicates that epithelial-to-mesenchymal (EMT)-like transitions occurred in cKO tumors. We performed microarray analysis on these tumors and found changes that support EMT-like changes. We established primary tumor cell lines and found that BMPR1a cKO had slower growth in vitro and in vivo upon implantation. cKO tumor cells had reduced migration in vitro. We analyzed human databases from TCGA and survival data from microarrays to confirm BMPR1a tumor promoting functions, and found that high BMPR1a gene expression correlates with decreased survival regardless of molecular breast cancer subtype. In conclusion, the data indicate that BMP signaling through BMPR1a functions as a tumor promoter.

MeSH Terms (9)

Animals Bone Morphogenetic Protein Receptors, Type I Breast Neoplasms Humans Mice Mice, Inbred C57BL Microarray Analysis Neoplasm Metastasis Signal Transduction

Connections (3)

This publication is referenced by other Labnodes entities:

Links