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:
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Authors | Felix Rückert, Peer Joensson, Hans-Detlev Saeger, Robert Grützmann, Christian Pilarsky |
Journal | International journal of colorectal disease
(Int J Colorectal Dis)
Vol. 25
Issue 3
Pg. 303-11
(Mar 2010)
ISSN: 1432-1262 [Electronic] Germany |
PMID | 20012301
(Publication Type: Journal Article)
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Chemical References |
- E2F5 Transcription Factor
- E2F5 protein, human
- RNA, Small Interfering
- Deoxycytidine
- Amino Acid Oxidoreductases
- LOXL2 protein, human
- Gemcitabine
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Topics |
- Amino Acid Oxidoreductases
(genetics, metabolism)
- Cell Death
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Deoxycytidine
(analogs & derivatives, pharmacology)
- Drug Resistance, Neoplasm
(drug effects)
- E2F5 Transcription Factor
(genetics, metabolism)
- Epithelium
(drug effects, metabolism, pathology)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Gene Knockdown Techniques
- Gene Silencing
(drug effects)
- Humans
- Mesoderm
(drug effects, metabolism, pathology)
- Pancreatic Neoplasms
(enzymology, genetics, pathology)
- RNA, Small Interfering
(metabolism)
- Stress, Physiological
(drug effects)
- Transfection
- Gemcitabine
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