Carcinogenesis Advance Access originally published online on April 11, 2007
Carcinogenesis 2007 28(8):1638-1645; 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
1 Cell Signalling Unit at the Department of Biomorphology, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
2 Laboratory of Cytomorphology, Center for Ageing Sciences (Ce.S.I.), "Università G.d'Annunzio" Foundation, Chieti, Italy
3 Section of Morbid Anatomy, Histopathology and Cytopathology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy
* To whom correspondence should be addressed. Tel: +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 histopathological 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 with 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.
Abbreviations: MFI, mean fluorescent intensity; PBS, phosphate-buffered saline; PI, propidium iodide; PLC, phospholipase C
Received September 22, 2006; revised February 16, 2007; accepted March 27, 2007.
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