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Cited by 23Cancer Cells and MetastasisMechanisms of cancer metastasisBreast Cancer Treatment Studies

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

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Krstic, Milica, Macmillan, Connor D., Leong, Hon S., Clifford, Allen G., Souter, Lesley H., Dales, David W., Postenka, Carl O., Chambers, Ann F. +1 more·2016·BMC Cancer
DOI 10.1186/s12885-016-2697-zPMC PMC4994202
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Abstract

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.

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Cited by

Sorted by citations

Authors
Krstic, M., Macmillan, C. D., Leong, H. S., Clifford, A. G., Souter, L. H., Dales, D. W., Postenka, C. O., Chambers, A. F., & Tuck, A. B.
Affiliations
Western University (CA)
Corresponding author
Tuck, Alan B.
ORCID
Venue
BMC Cancer
Publisher
Springer Science and Business Media LLC
Published
2016-08-23
Volume
16
Issue
1
Pages
671-671
ISSN
1471-2407 (ISSN-L)
DOI
10.1186/s12885-016-2697-z
PMC
PMC4994202
OpenAlex
W2507779429
Cited by
23
References
2
Citations by year
2025: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 3
FWCI
2.16
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Cancer (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Movember Foundation
  • Breast Cancer Society of Canada
  • Canada Research Chairs
  • Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
TBX3, breast cancer progression, T-box transcription factor, ductal carcinoma in situ, atypical ductal hyperplasia, epithelial-mesenchymal transition, tumor invasion, cell survival, colony formation, gene expression profiling, metastatic breast cancer
MeSH terms
Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Collagen, Drug Combinations, Female, Humans, Hyperplasia, Laminin, Neoplasm Invasiveness, Proteoglycans, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Carcinoma, Ductal, Breast, Disease Progression, Protein Isoforms, T-Box Domain Proteins, RNA, Small Interfering, Epithelial-Mesenchymal Transition

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