- Paper Report
- Open Access
bcl-2: a convergence point for multiple signal transduction pathways that influence cell survival?
- Julia MW Gee1
© Biomed Central Ltd 2002
- Received: 14 January 2002
- Published: 1 December 2002
- bcl-2, breast cancer, cell survival, mcl-1, signal transduction inhibitors
Members of the bcl-2 family of proteins, such as bcl-2 and mcl-1, have been implicated in controlling cell survival in many normal and neoplastic cells in a tissue-specific manner. Delineating those family members of relevance to breast cancer and manipulation of their regulatory signalling pathways is therapeutically attractive. The aim of this study, performed in MCF-7 human breast cancer cells, was to determine whether inhibition of protein tyrosine kinase, protein kinase C, phosphatidylinositol 3-kinase or mitogen-activated protein kinase kinase (MEK) signal transduction influences expression of bcl-2 or mcl-1, monitoring cytotoxicity in parallel.
The authors observed that, while there were only limited changes in mcl-1, the examined signal transduction inhibitors (i.e. genistein, staurosporine, LY294002 and U0126) downregulated bcl-2 protein expression in a dose-dependent manner. In parallel, such agents were highly growth inhibitory, arresting cell cycle and increasing cell death. Synergistic cytotoxic activity was observed between the MEK inhibitor UO126 and other agents. The authors concluded that bcl-2, in contrast to mcl-1, plays a predominant role in the control of cell survival by diverse signal transduction pathways in MCF-7 cells.
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