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Essential role of STAT5a in DCIS formation and invasion following estrogen treatment.
- Source :
-
Aging [Aging (Albany NY)] 2020 Aug 05; Vol. 12 (14), pp. 15104-15120. - Publication Year :
- 2020
-
Abstract
- Ductal carcinoma in situ (DCIS) is one of the earliest stages of breast cancer (BCa). The mechanisms by which DCIS lesions progress to an invasive state while others remain indolent are yet to be fully characterized and both diagnosis and treatment of this pre-invasive disease could benefit from better understanding the pathways involved. While a decreased expression of Caveolin-1 (Cav-1) in the tumor microenvironment of patients with DCIS breast cancer was linked to progression to invasive breast cancer (IBC), the downstream effector(s) contributing to this process remain elusive. The current report shows elevated expression of Signal Transducer and Activator of Transcription 5a (STAT5a) within the DCIS-like lesions in Cav-1 KO mice following estrogen treatment and inhibition of STAT5a expression prevented the formation of these mammary lesions. In addition, STAT5a overexpression in a human DCIS cell line (MCF10DCIS.com) promoted their invasion, a process accelerated by estrogen treatment and associated with increased levels of the matrix metalloproteinase-9 (MMP-9) precursor. In sum, our results demonstrate a novel regulatory axis (Cav-1♦STAT5a♦MMP-9) in DCIS that is fully activated by the presence of estrogen. Our sudies suggest to further study phosphorylated STAT5a (Y694) as a potential biomarker to guide and predict outcome of DCIS patient population.
- Subjects :
- Animals
Biomarkers, Tumor analysis
Cell Line, Tumor
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Matrix Metalloproteinase 9 metabolism
Mice
Phosphorylation
Tumor Microenvironment
Breast Neoplasms metabolism
Breast Neoplasms pathology
Carcinoma, Intraductal, Noninfiltrating metabolism
Carcinoma, Intraductal, Noninfiltrating pathology
Caveolin 1 metabolism
Estrogens metabolism
Estrogens pharmacology
Neoplasm Invasiveness genetics
Neoplasm Invasiveness prevention & control
STAT5 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-4589
- Volume :
- 12
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Aging
- Publication Type :
- Academic Journal
- Accession number :
- 32633727
- Full Text :
- https://doi.org/10.18632/aging.103586