The transcriptional regulator TBX3 promotes progression from non-invasive to invasive breast cancer

Autor: Ann F. Chambers, Milica Krstic, Allen G. Clifford, Alan B. Tuck, David W. Dales, Hon S. Leong, Connor D. MacMillan, Lesley H. Souter, Carl O. Postenka
Jazyk: angličtina
Předmět:
0301 basic medicine
CA15-3
Pathology
medicine.medical_specialty
Cancer Research
Epithelial-Mesenchymal Transition
Cell
Breast Neoplasms
03 medical and health sciences
Breast cancer
Invasive mammary carcinoma
Tumor Cells
Cultured
Genetics
Humans
Protein Isoforms
Medicine
Neoplasm Invasiveness
Epithelial–mesenchymal transition
RNA
Small Interfering
Matrigel
Hyperplasia
business.industry
Carcinoma
Ductal
Breast
Ductal carcinoma in situ
TBX3
Ductal carcinoma
medicine.disease
Metastatic breast cancer
3. Good health
Gene Expression Regulation
Neoplastic
Drug Combinations
Carcinoma
Intraductal
Noninfiltrating
030104 developmental biology
medicine.anatomical_structure
Oncology
Cell culture
Disease Progression
Cancer research
Female
Proteoglycans
Collagen
Laminin
T-Box Domain Proteins
business
Research Article
Zdroj: BMC Cancer
ISSN: 1471-2407
DOI: 10.1186/s12885-016-2697-z
Popis: Background TBX3 is a T-box transcription factor repressor that is elevated in metastatic breast cancer and is believed to promote malignancy of tumor cells, possibly by promoting cell survival and epithelial-mesenchymal transition. Methods The relative expression of TBX3 was assessed in the 21T cell lines which were derived from an individual patient and represent three distinct stages of breast cancer progression: 21PT, atypical ductal hyperplasia; 21NT, ductal carcinoma in situ; and 21MT-1, invasive mammary carcinoma. Two different isoforms of TBX3 (TBX3iso1 and TBX3iso2) were overexpressed to evaluate cell survival/colony forming ability, growth, and invasion in the ductal carcinoma in situ-like 21NT cell line using an in vitro Matrigel model of cancer progression. In addition, TBX3 expression was knocked down to evaluate the effects of downregulating TBX3 on the invasive mammary carcinoma-like 21MT-1 cell line. Finally, PCR array profiling was used to assess alterations in gene expression due to TBX3 overexpression in the 21NT cells. Results TBX3 is abundant in the invasive 21MT-1 cell line, while being minimally expressed in the non-invasive 21NT and 21PT cell lines. Overexpression of either TBX3iso1 or TBX3iso2 in 21NT cells resulted in increased cell survival/colony forming ability, growth vs. apoptosis and invasion in Matrigel. In contrast, short hairpin RNA-mediated knockdown of TBX3 in the 21MT-1 cells resulted in smaller colonies, with a more regular, less dispersed (less infiltrative) morphology. Array profiling of the 21NT TBX3 iso1 and iso2 transfectants showed that there are common alterations in expression of several genes involved in signal transduction, cell cycle control/cell survival, epithelial-mesenchymal transition and invasiveness. Conclusions Overall, these results indicate that TBX3 (isoform 1 or 2) expression can promote progression in a model of early breast cancer by altering cell properties involved in cell survival/colony formation and invasiveness, as well as key regulatory and EMT/invasiveness-related gene expressions.
Databáze: OpenAIRE
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