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:C0027627 (
metastases
)
103,950
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Metastasis
in breast cancer carries a disproportionately worse prognosis than localized primary disease. To identify microRNAs (miRNA) involved in metastasis, the expression of 254 miRNAs was measured across the following cell lines using microarray analysis: MDA-MB-231 breast cancer cells, cells that grew as a tumor in the mammary fat pad of nude mice (TMD-231),
metastatic disease
to the lungs (LMD-231), bone (BMD-231) and adrenal gland (ADMD-231). A brain-seeking variant of this cell line (231-BR) was used additionally in validation studies. Twenty miRNAs were upregulated and seven were downregulated in
metastatic cancer
cells compared with TMD-231 cells. The expression of the tumor suppressor miRNAs let-7 and miR-22 was consistently downregulated in
metastatic cancer
cells. These metastatic cells expressed higher levels of putative/proven miR-22 target oncogenes ERBB3, CDC25C and EVI-1. Introduction of miR-22 into cancer cells reduced the levels of ERBB3 and EVI-1 as well as phospho-AKT, an EVI-1 downstream target. The miR-22 primary transcript is located in the 5'-untranslated region of an open reading frame
C17orf91
, and the promoter/enhancer of
C17orf91
drives miR-22 expression. We observed elevated
C17orf91
expression in non-basal subtype compared with basal subtype breast cancers. In contrast, elevated expression of EVI-1 was observed in basal subtype and was associated with poor outcome in estrogen receptor-negative breast cancer patients. These results suggest that
metastatic cancer
cells increase specific oncogenic signaling proteins through downregulation of miRNAs. Identifying such metastasis-specific oncogenic pathways may help to manipulate tumor behavior and aid in the design of more effective targeted therapies.
...
PMID:Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. 2105 39
