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Depletion of the Transcriptional Coactivator Amplified in Breast Cancer 1 (AIB1) Uncovers Functionally Distinct Subpopulations in Triple-Negative Breast Cancer
- Source :
- Neoplasia (New York, N.Y.), Neoplasia: An International Journal for Oncology Research, Vol 21, Iss 10, Pp 963-973 (2019)
- Publication Year :
- 2019
- Publisher :
- Neoplasia Press, 2019.
-
Abstract
- The transcriptional coactivator Amplified in Breast Cancer 1 (AIB1) plays a major role in the progression of hormone and HER2-dependent breast cancers but its role in triple negative breast cancer (TNBC) is undefined. Here, we report that established TNBC cell lines, as well as cells from a TNBC patient-derived xenograft (PDX) that survive chemotherapy treatment in vitro express lower levels of AIB1 protein. The surviving cell population has an impaired tube-formation phenotype when cultured onto basement membrane, a property shared with TNBC cells that survive shRNA-mediated depletion of AIB1 (AIB1LOW cells). DNA analysis by exome sequencing revealed that AIB1LOW cells represent a distinct subpopulation. Consistent with their in vitro phenotype AIB1LOW cells implanted orthotopically generated slower growing tumors with less capacity for pulmonary metastases. Gene expression analysis of cultured cells and tumors revealed that AIB1LOW cells display a distinct expression signature of genes in pro-inflammatory pathways, cell adhesion, proteolysis and tissue remodeling. Interestingly, the presence of this AIB1LOW expression signature in breast cancer specimens is associated with shorter disease free survival of chemotherapy treated patients. We concluded that TNBC cell lines contain heterogeneous populations with differential dependence on AIB1 and that the gene expression pattern of AIB1LOW cells may represent a signature indicative of poor response to chemotherapy in TNBC patients.
- Subjects :
- 0301 basic medicine
Cancer Research
Original article
Cell
Population
Triple Negative Breast Neoplasms
Biology
lcsh:RC254-282
Transcriptome
Clonal Evolution
Nuclear Receptor Coactivator 3
03 medical and health sciences
Mice
0302 clinical medicine
Breast cancer
Cell Line, Tumor
Exome Sequencing
medicine
Animals
Humans
RNA, Small Interfering
education
Triple-negative breast cancer
Regulation of gene expression
education.field_of_study
Gene Expression Profiling
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
3. Good health
Gene expression profiling
Gene Expression Regulation, Neoplastic
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Phenotype
Cell culture
030220 oncology & carcinogenesis
Cancer research
Heterografts
Female
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 14765586 and 15228002
- Volume :
- 21
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Neoplasia (New York, N.Y.)
- Accession number :
- edsair.doi.dedup.....81083062ae09f57de7475e5c1d105dde