TGFβ-induced c-Myb affects the expression of EMT-associated genes and promotes invasion of ER

Vincenzo Cesi, Arianna Casciati, Fabiola Sesti, Barbara Tanno, Bruno Calabretta, Giuseppe Raschellà

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Advanced breast cancer cells acquire metastatic properties in response to TGFβ. We show here that the expression of c-Myb increases in TGFβ-treated ER+breast cancer cells by protein stabilization, transcription activation and release from miR200-dependent downregulation. In particular, we mapped two sites for miR200b, miR200c and miR429 binding in the 3′ UTR of the human c-myb gene. These microRNAs decreased the expression of c-Myb when transfected in MCF-7 cells. In addition, luciferase activity from a vector containing the 3′ UTR of the c-myb gene was inhibited by miR200s through a binding-dependent mechanism. siRNA- and shRNA-mediated downregulation was used to investigate the role of c-Myb for the effects induced by TGFβ in ER+breast cancer MCF-7 and ZR-75.1 cells. Transfection with c-Myb siRNAs blocked the increase of Slug (SNAI2) and Bcl-2 expression and reversed the decrease in E-cadherin expression induced by TGFβ treatment. Conversely, c-Myb downregulation decreased invasion and anchorage-independent growth of breast cancer cells expressing a constitutively active TGFβ receptor I. Finally, apoptosis induced by etoposide increased in c-Myb-silenced TGFβ-treated ER+cell lines. In summary, exposure of ER+breast cancer cells to TGFβ induces an increase of c-Myb expression, which is required for expression of EMT-associated markers, in vitro invasion and anchorage-independent growth. Furthermore, our findings suggest a potentially detrimental effect of TGFβ and c-Myb co-expression in breast cancer. © 2011 Landes Bioscience.
Original languageEnglish
Pages (from-to)4149 - 4161
Number of pages13
JournalCell Cycle
Volume10
Issue number23
DOIs
Publication statusPublished - 1 Dec 2011
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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