title: Runx1 is associated with breast cancer progression in MMTV-PyMT transgenic mice and its depletion in vitro inhibits migration and invasion.
abstract: Runx1 is a transcription factor essential for definitive hematopoiesis, and genetic abnormalities in Runx1 cause leukemia. Runx1 is functionally promiscuous and acts as either an oncogene or tumor suppressor gene in certain epithelial cancers. Recent evidence suggests that Runx1 is an important factor in breast cancer, however, its role remains ambiguous. Here, we addressed whether Runx1 has a specific pathological role during breast cancer progression and show that Runx1 has an oncogenic function. We observed elevated Runx1 expression in a subset of human breast cancers. Furthermore, throughout the course of disease progression in a classical mouse model of breast cancer (i.e., the MMTV-PyMT transgenic model), Runx1 expression increases in the primary site (mammary gland) and is further upregulated in tumors and distal lung metastatic lesions. Ex vivo studies using tumor epithelial cells derived from these mice express significantly higher levels of Runx1 than normal mammary epithelial cells. The tumor cells exhibit increased rates of migration and invasion, indicative of an aggressive cancer phenotype. Inhibition of Runx1 expression using RNA interference significantly abrogates these cancer-relevant phenotypic characteristics. Importantly, our data establish that Runx1 contributes to murine mammary tumor development and malignancy and potentially represents a key disease-promoting and prognostic factor in human breast cancer progression and metastasis.
authors: Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont.|Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Gillian
authors: G
authors: Browne
authors: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts.|Heisenberg-Group for Molecular Skeletal Biology, Department of Trauma, Hand & Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Hanna
authors: H
authors: Taipaleenmäki
authors: Microscopy Imaging Center, University of Vermont College of Medicine, Burlington, Vermont.
authors: Nicole M
authors: NM
authors: Bishop
authors: Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont.
authors: Sharath C
authors: SC
authors: Madasu
authors: Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Leslie M
authors: LM
authors: Shaw
authors: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts.|Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota.
authors: Andre J
authors: AJ
authors: van Wijnen
authors: Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont.|Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Janet L
authors: JL
authors: Stein
authors: Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont.|Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Gary S
authors: GS
authors: Stein
authors: Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont.|Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts.
authors: Jane B
authors: JB
authors: Lian
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse