Epigenetic control of endothelin-1 axis affects invasiveness of breast carcinoma cells with bone tropism

Emanuela Matteucci, Paola Maroni, Paola Bendinelli, Alessia Locatelli, Maria Alfonsina Desiderio

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Here, we report a complex regulation of endothelin-1 (ET-1) axis driven by epigenetic reactions in 1833-bone metastatic cells, emphasizing the importance in skeletal metastasis from breast carcinoma. Inhibitors of histone deacetylases, trichostatin A (TSA), and of DNA methylases, 5'-Azacytidine (Aza), caused, respectively, reduction and increase in 1833 cell invasiveness, without affecting the basal migration of parental MDA-MB231 cells. Of note, in the two cell lines exposed to Aza the blockade of the ET-1 receptor ETAR with BQ-123 oppositely changed invasive properties. Even if in MDA-MB231 cells the ET-1 axis was scarcely influenced by epigenetic reactions, ETAR remarkably decreased after Aza. In contrast, in 1833 cells Aza exposure enhanced ET-1 coupled to ETAR wild type, being also ETAR truncated form increased, and invasiveness was stimulated. Under demethylation, the increase in ET-1 steady state protein level in 1833 clone seemed regulated at transcriptional level principally via Ets1 transcription factor. In fact, actinomycin D almost completely prevented ET-1 mRNA induction due to Aza. Only in 1833 cells, TSA exposure inactivated ET-1 axis, with reduction of the expression of ET-1 and ETAR mutated form, in agreement with Matrigel invasion decrease. This treatment favoured the ET-1 repressional control, taking place at the level of mRNA stability due to the 3'-untranslated region in the ET-1 gene, and also decreased transcription via NF-kB. Environmental conditions that alter the balance between epigenetic reactions might, therefore, affect metastasis migratory mode influencing ET-1 axis.

Original languageEnglish
Pages (from-to)1865-1874
Number of pages10
JournalExperimental Cell Research
Volume319
Issue number12
DOIs
Publication statusPublished - Jul 15 2013

Fingerprint

Tropism
Endothelin-1
Epigenomics
Breast Neoplasms
Azacitidine
Bone and Bones
trichostatin A
Neoplasm Metastasis
Endothelin A Receptors
Histone Deacetylases
NF-kappa B
RNA Stability
3' Untranslated Regions
Dactinomycin
Transcription Factors
Clone Cells
Cell Line
Messenger RNA

Keywords

  • Bone metastasis
  • DNA methylation
  • Endothelin axis
  • ETR
  • HDACs

ASJC Scopus subject areas

  • Cell Biology

Cite this

Epigenetic control of endothelin-1 axis affects invasiveness of breast carcinoma cells with bone tropism. / Matteucci, Emanuela; Maroni, Paola; Bendinelli, Paola; Locatelli, Alessia; Desiderio, Maria Alfonsina.

In: Experimental Cell Research, Vol. 319, No. 12, 15.07.2013, p. 1865-1874.

Research output: Contribution to journalArticle

Matteucci, Emanuela ; Maroni, Paola ; Bendinelli, Paola ; Locatelli, Alessia ; Desiderio, Maria Alfonsina. / Epigenetic control of endothelin-1 axis affects invasiveness of breast carcinoma cells with bone tropism. In: Experimental Cell Research. 2013 ; Vol. 319, No. 12. pp. 1865-1874.
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