JAI PARKASH and KAMLESH ASOTRA,

Robert Stempel College of Public Health and Social Work, Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, HLS-594, Miami, FL 33199, USA

Tobacco-Related Disease Research Program University of California Office of President 300 Lakeside Drive Oakland, CA 94612, USA Tel: (510) 287-3366 FAX: (510) 835-4740 kamlesh.asotra@ucop.edu

Ca2+ functions as an important signaling messenger right from the beginning of the life to final moment of the end of the life. Ca2+ is needed at several steps of the cell cycle such as early G1, at the G1/S, and G2/M transitions. The Ca2+ signals in the form of time-dependent changes in intracellular Ca2+ concentrations, [Ca2+]i, are presented as brief spikes organized into regenerative Ca2+ waves. Ca2+-mediated signaling pathways have also been shown to play important roles in carcinogeneses such as the transformation of normal cells to cancerous cells, tumor formation and growth, invasion, angiogenesis, and metastasis. Since the global Ca2+ oscillations arise from Ca2+ waves initiated locally, it results in stochastic oscillations because although each cell has many IP3Rs and Ca2+ ions, the law of large numbers does not apply to the initiating event which is restricted to very few IP3Rs due to steep Ca2+ concentration gradients. The specific Ca2+ signaling information is likely to be encoded in a calcium code as the amplitude, duration, frequency, waveform or timing of Ca2+ oscillations and decoded again at a later stage. Since Ca2+ channels or pumps involved in regulating Ca2+ signaling pathways show altered expression in cancer, one can
target these Ca2+ channels and pumps as therapeutic options to decrease proliferation of cancer cells and to promote their apoptosis. These studies can provide novel insights into alterations in Ca2+ wave patterns in carcinogenesis and lead to the development of newer technologies based on Ca2+ waves for the diagnosis and therapy of cancer.