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Role of ornithine decarboxylase in breast cancer
Wensheng Deng1, Xian Jiang, Yu Mei
1Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.
Abstract:
Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis that decarboxylates ornithine to putrescine, has become a promising target for cancer research. The aim of this study is to investigate the role of ODC in breast cancer. We detected expression of ODC in breast cancer tissues and four breast cancer cell lines, and transfected breast cancer cells with an adenoviral vector carrying antisense ODC (rAd-ODC/Ex3as) and examined their growth and migration. ODC was overexpressed in breast cancer tissues and cell lines compared with non-tumor tissues and normal breast epithelial cells, and there was a positive correlation between the level of ODC mRNA and the staging of tumors. The expression of ODC correlated with cyclin D1, a cell cycle protein, in synchronized breast cancer MDA-MB-231 cells. Gene transfection of rAd-ODC/Ex3as markedly down-regulated expression of ODC and cyclin D1, resulting in suppression of proliferation and cell cycle arrest at G0-G1 phase, and the inhibition of colony formation, an anchorage-independent growth pattern, and the migratory ability of MDA-MB-231 cells. rAd-ODC/Ex3as also markedly reduced the concentration of putrescine, but not spermidine or spermine, in MDA-MB-231 cells. The results suggested that the ODC gene might act as a prognostic factor for breast cancer and it could be a promising therapeutic target.
Insights
Ornithine decarboxylase (ODC) is overexpressed in breast cancer, correlating with tumor stage. Inhibiting ODC suppressed cancer cell proliferation and migration, suggesting it
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis, converting ornithine to putrescine.
- Polyamines play crucial roles in cell growth and proliferation, making ODC a potential target in cancer research.
Purpose of the Study:
- To investigate the role of Ornithine decarboxylase (ODC) in breast cancer.
- To evaluate ODC as a potential therapeutic target for breast cancer treatment.
Main Methods:
- Detection of ODC expression in breast cancer tissues and cell lines.
- Transfection of breast cancer cells with an adenoviral vector carrying antisense ODC (rAd-ODC/Ex3as).
- Assessment of cell proliferation, cell cycle, colony formation, and migration.
Main Results:
- ODC was overexpressed in breast cancer tissues and cell lines, with higher levels correlating with advanced tumor stage.
- Down-regulation of ODC using rAd-ODC/Ex3as suppressed proliferation, induced G0-G1 cell cycle arrest, and inhibited colony formation and migration.
- ODC inhibition reduced putrescine levels but did not affect spermidine or spermine concentrations.
Conclusions:
- ODC overexpression is linked to breast cancer progression.
- ODC acts as a prognostic factor and a potential therapeutic target for breast cancer.
- Targeting ODC may offer a novel strategy for breast cancer treatment.
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