Carcinogenesis Advance Access published online on April 11, 2007
Carcinogenesis, doi:10.1093/carcin/bgm078
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Phospholipase C-ß2 promotes mitosis and migration of human breast cancer derived cells
Signal Transduction Unit, Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy
1 Section of Morbid Anatomy, Histopathology and Cytopathology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy
2 Cell Signalling Unit at the Department of Biomorphology, University "G. d'Annunzio" Chieti- Pescara, Chieti, Italy
Corresponding author: Silvano Capitani, Signal Transduction Unit/Laboratory of Cell Biology, Section of Human Anatomy-Department of Morphology and Embryology, Via Fossato di Mortara, 66, 44100 Ferrara, Italy. Phone: +39 0532 291571 Fax: +39 0532 207351, Email: cps{at}unife.it
Like most human neoplasm, breast cancer has aberrations in signal transduction elements that can lead to increased proliferative potential, apoptosis inhibition, tissue invasion and metastasis. Due to the high heterogeneity of this tumor, currently, no markers are clearly associated with the insurgence of breast cancer, as well as with its progression from in situ lesion to invasive carcinoma.
We have recently demonstrated an altered expression of the ß2 isoform of the phosphoinositide-dependent phospholipase C (PLC) in invasive breast tumors with different histo-pathological features. In primary breast tumor cells, elevated amounts of this protein are closely correlated with a poor prognosis of patients with mammary carcinoma, suggesting that PLC-ß2 may be involved in the development and worsening of the malignant phenotype.
Here we demonstrate that PLC-ß2 may improve some malignant characteristics of tumor cells, like motility and invasion capability, but it fails to induce tumorigenesis in non-transformed breast-derived cells. We also report that, compared to the G0/G1 phases of the cell cycle, the cells in S/G2/M phases show high PLC-ß2 expressions that reach the greatest levels during the late mitotic stages. In addition, even if unable to modify the proliferation rate and the expression of cell cycle related enzymes of malignant cells, PLC-ß2 may promote the G2/M progression, a critical event in cancer evolution. Since phosphoinositides, substrates of PLC, are involved in regulating cytoskeleton architecture, PLC-ß2 in breast tumor cells may mediate the modification of cell shape that characterizes cell division, motility and invasion.
On the basis of these data, PLC-ß2 may constitute a molecular marker of breast tumor cells able to monitor the progression to invasive cancers and a target for novel therapeutic breast cancer strategies.
Key Words: breast cancer • phospholipase C-ß2 (PLC-ß2) • cell migration and invasiveness • cell cycle • tumor progression
Received September 22, 2006; revised February 16, 2007; accepted March 27, 2007.
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