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




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Molecular Cancer

, 9:300

First Online: 23 November 2010Received: 23 February 2010Accepted: 23 November 2010

Abstract

BackgroundBasal-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.

ResultsHere 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.

ConclusionWe 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.

AbbreviationsNSFnon specific fragment

PDPrimer dimers.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-9-300 contains supplementary material, which is available to authorized users.

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Author: Laura D-Anello - Pasquale Sansone - Gianluca Storci - Valentina Mitrugno - Gabriele D-Uva - Pasquale Chieco - Massimiliano 

Source: https://link.springer.com/







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