Proteomic Analysis of Potential Breast Cancer Biomarkers

1.1 Cell signalling and tumorigenesis In multi-cellular organisms, cells have to communicate with each other in order to control their proliferation, differentiation, survival and to perform diverse physiological functions. Cells release and receive signals to induce these different states of growth either by direct cell-to-cell interaction or via secreted molecules. This communication is elicited through socalled signaling molecules such as transmembrane receptors that are embedded in cell membrane and can activate intracellular signal transduction cascades which ultimately lead to gene activation or repression and a cellular response. According to the specificity, strength and duration of the signal received, the cell will proliferate, differentiate, change shape, migrate, and enter into growth arrest or undergo apoptosis. These complex signaling networks are highly regulated and alterations of the normal intracellular signals can lead to the development of diseases such as cancer. It is now known that a series of genetic mutations are required for the progressive conversion of normal human cells into cancerous cells. Hanahan and Weinberg have proposed a model of tumorigenesis, whereby several physiological conditions are required before cells become tumorigenic (Hanahan and Weinberg, 2011). These include self-sufficiency in growth signals, insensitivity to growthinhibitory signals, evasion of programmed cell death, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis. In proliferative signaling pathways for example, numerous proto-oncogenes or tumor suppressors have been identified, the mutation of which cause amplification of signaling or loss of negative regulation resulting in over-proliferation and eventual tumor formation. Unlike normal cells, which tightly regulate extracellular ligand levels, receptor expression and secondary signaling molecules, cancer cells often lose the ability to regulate these signaling events. For example, overexpression of receptor tyrosine kinases (RTKs) (Libermann et al., 1985), mutation of RAt Sarcoma (Ras) protein (Marshall, 1996) or the overexpression of PI3K (phosphatidylinositol 3-kinase) (Sulis and Parsons, 2003) are thought to lead to cell transformation.