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Functional analysis of LOXL2 in pancreatic carcinoma

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Objectives

Lysyl oxidase-like 2 (LOXL2) plays a part in epithelial–mesenchymal transition (EMT) by stabilizing the transcription factor SNAI1. Previous studies showed that LOXL2 is one of the most highly and specifically upregulated genes in pancreatic cancer. LOXL2 was also found to be strongly upregulated in the secretome of established pancreatic cancer cell lines. To get more insight into the aggressive growth and infiltrating nature of pancreatic cancer, we evaluated the functional role of LOXL2 in pancreatic cancer cells.

Methods

Gene inhibition by small interfering RNAs was used to silence LOXL2 in pancreatic cancer cell lines MiaPaCa-2 and Panc1. Cell death, proliferation, and morphology of transfected cells were determined. Cell characteristics under cell stress and gemcitabine treatment were analyzed. Gene expression analysis of transfected cells by DNA microarray was used to understand the processes of chemosensitization.

Results

Silencing of LOXL2 in pancreatic cancer cells resulted in an augmented sensitivity toward gemcitabine treatment, with significantly elevated cell death and reduced viable cells. However, transfection had no direct effect on morphology or growth pattern of Mia PaCa-2 and Panc1 cell lines. Gene expression analysis identified among others the transcription factor E2F5 as possible target of LOXL2.

Conclusions

Gene inhibition of the EMT regulatory gene LOXL2 resulted in a distinct sensitization toward gemcitabine. Additionally, gene expression analysis showed a role for LOXL2 in the regulation of different transcription factors associated with invasion and metastasis. Our results suggest that the improved response toward chemotherapy in LOLX2-silenced pancreatic cancer cells is possibly mediated by the transcription factor E2F5.

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Authors and Affiliations

  1. Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstr. 74, 01307, Dresden, Germany

    Felix Rückert, Hans-Detlev Saeger, Robert Grützmann & Christian Pilarsky

  2. Department of Surgery I, Charité-Medical School, Campus Benjamin Franklin, Berlin, Germany

    Peer Joensson

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  1. Felix Rückert
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  3. Hans-Detlev Saeger
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  4. Robert Grützmann
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  5. Christian Pilarsky
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Correspondence to Felix Rückert.

Additional information

Robert Grützmann and Christian Pilarsky share the senior authorship for this work.

Felix Rükert and Peer Joensson contributed equally to this paper.

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Rückert, F., Joensson, P., Saeger, HD. et al. Functional analysis of LOXL2 in pancreatic carcinoma. Int J Colorectal Dis 25, 303–311 (2010). https://doi.org/10.1007/s00384-009-0853-5

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