Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0153690 (
bone metastases
)
6,382
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The skeleton is a preferred site of metastasis in patients with disseminated breast cancer. We have used 4T1 mouse mammary carcinoma cells, which metastasize to bone from the mammary fat pads of immunocompetent mice, to identify novel genes involved in this process. In vivo selection of parental cells resulted in the isolation of independent, aggressively bone metastatic breast cancer populations with reduced metastasis to the lung. Gene expression profiling identified
osteoactivin
as a candidate that is highly and selectively expressed in aggressively bone metastatic breast cancer cells. These cells displayed enhanced migratory and invasive characteristics in vitro, the latter requiring sustained
osteoactivin
expression. Osteoactivin depletion in these cells, by small interfering RNA, also lead to a loss of matrix metalloproteinase-3 expression, whereas forced
osteoactivin
expression in parental 4T1 cells was sufficient to elevate matrix metalloproteinase-3 levels, suggesting that this matrix metalloproteinase may be an important mediator of
osteoactivin
function. Overexpression of
osteoactivin
in an independent, weakly bone metastatic breast cancer cell model significantly enhanced the formation of osteolytic
bone metastases
in vivo. Finally, high levels of
osteoactivin
expression in primary human breast cancers correlate with estrogen receptor-negative status and increasing tumor grade. Thus, we have identified
osteoactivin
as a protein that is expressed in aggressive human breast cancers and is capable of promoting breast cancer metastasis to bone.
...
PMID:Osteoactivin promotes breast cancer metastasis to bone. 1795 1
