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)
Transforming growth factor-beta1 (TGF-beta1) is a crucial molecule for stimulation of breast cancer invasion and formation of
bone metastases
. The molecular mechanisms of how TGF-beta1 mediates these effects have yet to be completely determined. We have found that activating transcription factor-3 (ATF-3) is strongly stimulated and its level is sustained by TGF-beta1 in highly invasive and metastatic human breast cancer (MDA-MB231) and in mouse mammary pad tumor cells (r3T).
ATF
-3 is also overexpressed in human primary breast cancer tissue. Overexpression of
ATF
-3 increased normal human mammary epithelial cell number and DNA synthesis suggesting a role for
ATF
-3 in cell proliferation. The functional role of
ATF
-3 in breast cancer progression was determined by the RNA interference technique. Knockdown of
ATF
-3 by
ATF
-3 shRNA in MDA-MB231 cells decreased expression of cell cycle gene, cyclin A1 in MDA-MB231 cells.
ATF
-3 shRNA also decreased expression of an invasive and metastatic gene, matrix metalloproteinase-13 (MMP-13; collagenase-3) in these cells. Chromatin immunoprecipitation experiments identified the direct physical interaction of
ATF
-3 protein on the human MMP-13 promoter. Thus, the dysregulation of
ATF
-3 by TGF-beta1 is likely to activate cyclin A1 and MMP-13 genes in breast cancer cells and that would be key to the subsequent cancer cell invasion and metastasis.
...
PMID:Transforming growth factor-beta1 regulation of ATF-3 and identification of ATF-3 target genes in breast cancer cells. 1958 87
