Abstract

BackgroundThe GABARAP family members (GABARAP, GABARAPL1/GEC1 and GABARAPL2 /GATE-16) are involved in the intracellular transport of receptors and the autophagy pathway. We previously reported that GABARAPL1 expression was frequently downregulated in cancer cells while a high GABARAPL1 expression is a good prognosis marker for patients with lymph node-positive breast cancer.MethodsIn this study, we asked using qRT-PCR, western blotting and epigenetic quantification whether the expression of the GABARAP family was regulated in breast cancer by epigenetic modifications.ResultsOur data demonstrated that a specific decrease of GABARAPL1 expression in breast cancers was associated with both DNA methylation and histone deacetylation and that CREB-1 recruitment on GABARAPL1 promoter was required for GABARAPL1 expression.ConclusionsOur work strongly suggests that epigenetic inhibitors and CREB-1 modulators may be used in the future to regulate autophagy in breast cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1761-4) contains supplementary material, which is available to authorized users.

Highlights

  • The GABAA-receptor associated protein (GABARAP) family members (GABARAP, GABARAPL1/GEC1 and GABARAPL2 /GATE-16) are involved in the intracellular transport of receptors and the autophagy pathway

  • Our results revealed an insignificant decrease of both GABARAP and GABARAPL2 mRNA levels in grade III breast cancers (BC) compared to non tumoral tissue (NT)

  • Similar differences were observed between non tumoral MCF-10A cells and MCF-7 BC cells since we showed a significant decrease of GABARAP and GABARAPL2 expression in MCF-7 cells but the highest decrease was observed for GABARAPL1

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Summary

Introduction

The GABARAP family members (GABARAP, GABARAPL1/GEC1 and GABARAPL2 /GATE-16) are involved in the intracellular transport of receptors and the autophagy pathway. Autophagy is a cell process which regulates cell homeostasis and survival by inducing the degradation and recycling of intracellular components like protein aggregates or organelles (such as damaged mitochondria) [1]. The analysis of GABARAPL1 expression in a cohort of 256 breast adenocarcinoma revealed that a low GABARAPL1 expression was correlated with a high risk of metastasis, in particular for lymph nodepositive patients [6]. Despite these recent studies, the regulation of the GABARAP family is still poorly understood and the origin of their decreased expression in tumor models remains unknown

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