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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

Authors: Laura D'Anello, Pasquale Sansone, Gianluca Storci, Valentina Mitrugno, Gabriele D'Uva, Pasquale Chieco, Massimiliano Bonafé

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα) and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6), a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells.

Results

Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα) promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions.

Conclusion

We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.
Appendix
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Metadata
Title
Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells
Authors
Laura D'Anello
Pasquale Sansone
Gianluca Storci
Valentina Mitrugno
Gabriele D'Uva
Pasquale Chieco
Massimiliano Bonafé
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-300

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