Characterization of GABARAP, a novel tumor suppressor, showing reduced expression in breast cancer

Klebig, Christiane; Deutschmann, Nicole; Pacyna-Gengelbach, Manuela; Seitz, Susanne; Scherneck, Siegfried; Petersen, Ivy A.

doi:10.1016/s0344-0338(04)80578-8

Cited by 41 publications

(57 citation statements)

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“…Our study showed that MCF-7 cells overexpressing GABARAPL1 protein had a significantly decreased growth rate, compared with control cell lines. This finding was in favour of a potential role of GABARAPL1 in the control of cell proliferation as previously reported for GABARAP overexpression in CAL51 cells (Klebig et al, 2005). These data suggested that gabarapl1 expression could be altered in rapidly growing breast tumour tissues.…”

Section: Discussionsupporting

confidence: 79%

“…Moreover, tissue microarray experiments revealed a significant reduction in GABARAP protein expression in a high proportion of 93 breast cancers cases (Klebig et al, 2005). However, no correlation was observed between loss of GABARAP expression and clinicopathological features such as grading, tumour size, oestrogen receptor status and age of diagnosis.…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, it was reported that lower levels of gabarap gene expression predict decreased survival among patients with neuroblastoma (Roberts et al, 2004). Klebig et al (2005) showed that an ectopic overexpression of the gabarap gene inhibits cancer cell proliferation and tumour growth in mice. We reported elsewhere a decrease in gabarapl1 expression in cancer cell lines (Nemos et al, 2003).…”

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confidence: 99%

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High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

et al. 2010

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BACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT -qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph nodepositive (pN þ ) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN þ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN þ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN þ patients.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 97%

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confidence: 99%

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High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

et al. 2010

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“…78 GABARAP also has a role in other cancers as GABARAP transcript expression correlates with a better survival rate for patients affected by neuroblastoma, 79 and GABARAP protein expression is significantly upregulated in colorectal cancer. 80 Autophagy has been described to play a paradoxical role in tumor apparition and progression.…”

Section: The Role Of Gabarapl1 In Neuronal Signal Transmissionmentioning

confidence: 99%

GABARAPL1 (GEC1): Original or copycat?

Grand

Chakrama²,

Seguin-Py³

et al. 2011

Autophagy

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“…The observation of abnormal GABARAP expression levels in cancer cells suggests a potential role of this protein during cancer development (8,9). Structural studies using nuclear magnetic resonance (NMR) spectroscopy as well as x-ray crystallography have revealed that most interactions of GABARAP are mediated by two hydrophobic pockets on its surface (10 -14), and that this binding site is also available in the lipidated form of the molecule (15).…”

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confidence: 99%

Interaction of Bcl-2 with the Autophagy-related GABAA Receptor-associated Protein (GABARAP)

Schwarten

Schneider

et al. 2013

Journal of Biological Chemistry

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Background: Apoptosis and autophagy are coordinately regulated, but the underlying mechanisms are incompletely understood. Results: Bcl-2 specifically interacts with GABARAP via a conserved EWD motif, resulting in impaired GABARAP lipidation. Conclusion: Sequestration of GABARAP is likely to contribute to the down-regulation of autophagy by Bcl-2. Significance: Interfering with pro-survival functions of Bcl-2 (including its impact on autophagy) represents a promising strategy for cancer therapy.

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Characterization of GABARAP, a novel tumor suppressor, showing reduced expression in breast cancer

Cited by 41 publications

References 0 publications

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

GABARAPL1 (GEC1): Original or copycat?

Interaction of Bcl-2 with the Autophagy-related GABAA Receptor-associated Protein (GABARAP)

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