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2 Growth Factors and Oncogenes

Robert A. Weinberg


Cells within a normal tissue undertake programs of growth and differentiation on the basis of signals received from other cells in the tissue or organism. This network of intercellular signaling represents the basis for establishing and maintaining normal tissue architecture. Many of the signals passing between cells appear to be carried by growth factors (GFs), which can influence cell growth in a positive or negative way. Growth factors are released in carefully measured amounts by some cells and are conveyed via several mechanisms to target cells. They are bound to specific receptors displayed by these target cells. This binding in turn triggers a complex signal transduction cascade that ultimately affects the cell’s decision to grow or to remain quiescent. Included in this cascade is the transduction of signals across the plasma membrane, the alteration of cytoplasmic proteins and low-molecular-weight “second-messenger” molecules, and finally, the transmission of signals to the nucleus where they affect the expression of critical genes involved in growth-controlling decisions.

The process of tumorigenesis represents a disruption of this complex signaling network. As a result, a cell may lose dependence on exogenous mitogenic growth factors and develop an autonomous mode of growth control. Some oncogenes intervene in this process by enabling a cell to grow even in the absence of the mitogenic growth factors that are usually required to trigger growth. Yet others may enable a cell to proliferate despite the presence of negative environmental signals that would normally act to inhibit cell growth. As described...

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