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Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system.

Publication ,  Journal Article
D'Amato, NC; Ostrander, JH; Bowie, ML; Sistrunk, C; Borowsky, A; Cardiff, RD; Bell, K; Young, LJT; Simin, K; Bachelder, RE; Delrow, J; Yee, LD ...
Published in: PLoS One
2012

Breast cancers with a basal-like gene signature are primarily triple-negative, frequently metastatic, and carry a poor prognosis. Basal-like breast cancers are enriched for markers of breast cancer stem cells as well as markers of epithelial-mesenchymal transition (EMT). While EMT is generally thought to be important in the process of metastasis, in vivo evidence of EMT in human disease remains rare. Here we report a novel model of human triple-negative breast cancer, the DKAT cell line, which was isolated from an aggressive, treatment-resistant triple-negative breast cancer that demonstrated morphological and biochemical evidence suggestive of phenotypic plasticity in the patient. The DKAT cell line displays a basal-like phenotype in vitro when cultured in serum-free media, and undergoes phenotypic changes consistent with EMT/MET in response to serum-containing media, a unique property among the breast cancer cell lines we tested. This EMT is marked by increased expression of the transcription factor Zeb1, and Zeb1 is required for the enhanced migratory ability of DKAT cells in the mesenchymal state. DKAT cells also express progenitor-cell markers, and single DKAT cells are able to generate tumorspheres containing both epithelial and mesenchymal cell types. In vivo, as few as ten DKAT cells are capable of forming xenograft tumors which display a range of epithelial and mesenchymal phenotypes. The DKAT model provides a novel model to study the molecular mechanisms regulating phenotypic plasticity and the aggressive biology of triple-negative breast cancers.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

9

Start / End Page

e45684

Location

United States

Related Subject Headings

  • Prognosis
  • Phenotype
  • Neoplasm Transplantation
  • Neoplasm Metastasis
  • Mice
  • Karyotyping
  • Humans
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling
 

Citation

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D’Amato, N. C., Ostrander, J. H., Bowie, M. L., Sistrunk, C., Borowsky, A., Cardiff, R. D., … Seewaldt, V. L. (2012). Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system. PLoS One, 7(9), e45684. https://doi.org/10.1371/journal.pone.0045684
D’Amato, Nicholas C., Julie H. Ostrander, Michelle L. Bowie, Christopher Sistrunk, Alexander Borowsky, Robert D. Cardiff, Katie Bell, et al. “Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system.PLoS One 7, no. 9 (2012): e45684. https://doi.org/10.1371/journal.pone.0045684.
D’Amato NC, Ostrander JH, Bowie ML, Sistrunk C, Borowsky A, Cardiff RD, et al. Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system. PLoS One. 2012;7(9):e45684.
D’Amato, Nicholas C., et al. “Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system.PLoS One, vol. 7, no. 9, 2012, p. e45684. Pubmed, doi:10.1371/journal.pone.0045684.
D’Amato NC, Ostrander JH, Bowie ML, Sistrunk C, Borowsky A, Cardiff RD, Bell K, Young LJT, Simin K, Bachelder RE, Delrow J, Dawson A, Yee LD, Mrózek K, Clay TM, Osada T, Seewaldt VL. Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system. PLoS One. 2012;7(9):e45684.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

9

Start / End Page

e45684

Location

United States

Related Subject Headings

  • Prognosis
  • Phenotype
  • Neoplasm Transplantation
  • Neoplasm Metastasis
  • Mice
  • Karyotyping
  • Humans
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
  • Gene Expression Profiling