Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer

Yelena Mironchik, Paul T. Winnard, Farhad Vesuna, Yoshinori Kato, Flonne Wildes, Arvind P. Pathak, Scott Kominsky, Dmitri Artemov, Zaver Bhujwalla, Paul Van Diest, Horst Burger, Carlotta Glackin, Venu Raman

Research output: Contribution to journalArticle

Abstract

Aggressive cancer phenotypes are a manifestation of many different genetic alterations that promote rapid proliferation and metastasis. In this study, we show that stable overexpression of Twist in a breast cancer cell line, MCF-7, altered its morphology to a fibroblastic-like phenotype, which exhibited protein markers representative of a mesenchymal transformation. In addition, it was observed that MCF-7/Twist cells had increased vascular endothelial growth factor (VEGF) synthesis when compared with empty vector control cells. The functional changes induced by VEGF in vivo were analyzed by functional magnetic resonance imaging (MRI) of MCF-7/Twist-xenografted tumors. MRI showed that MCF-7/Twist tumors exhibited higher vascular volume and vascular permeability in vivo than the MCF-7/vector control xenografts. Moreover, elevated expression of Twist in breast tumor samples obtained from patients correlated strongly with high-grade invasive carcinomas and with chromosome instability, particularly gains of chromosomes 1 and 7. Taken together, these results show that Twist overexpression in breast cancer cells can induce angiogenesis, correlates with chromosomal instability, and promotes an epithelial-mesenchymal-like transition that is pivotal for the transformation into an aggressive breast cancer phenotype.

Original languageEnglish (US)
Pages (from-to)10801-10809
Number of pages9
JournalCancer Research
Volume65
Issue number23
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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