PRINCIPLES OF TOXICOLOGY

lines of experimental evidence converged when it was shown that oncogenes that had been activated
by mutation with a carcinogenic chemical could transform normal cells into cancer cells. We now know
that the same oncogenes are often activated in tumors of the same cell type, whether the tumors arose
spontaneously or were virally or chemically induced.
A word about nomenclature should be mentioned here. The student may encounter several notations
associated with the names of oncogenes (oncs). The notation v-onc (e.g., v-sis) is used to distinguish
an oncogene of viral origin from a similar oncogene of cellular origin (c-onc, e.g., c-sis). It should also
be noted that not all oncogenes have been discovered in transforming retroviruses.
Oncogenes and Signal Transduction Pathways
13.4 MOLECULAR ASPECTS OF CARCINOGENESIS 281
To date, approximately 75 cellular oncogenes and their protooncogene counterparts have been
identified. The protein products of nearly all of these genes function in one way or another in cellular
signal transduction pathways to precisely regulate cell growth and differentiation. Signal transduction
pathways are used by cells to receive and process information and ultimately to effect a biological
response. These pathways generally consist of external signaling molecules, receptors on the cell
surface, transducer proteins, second messenger proteins, amplifier proteins, and effector proteins such
as transcription factors, all of which are involved in the regulation of cellular function or gene
expression. A generalized signal transduction pathway is shown in Figure 13.5. The protein products
of oncogenes have been grouped according to their function in several different categories (Table 13.5).
These categories include growth factors, growth factor receptors, membrane-associated GTP binding
proteins (G proteins), nonreceptor tyrosine kinases, cytoplasmic serine/threonine kinases, and nuclear
transcription factors. Activation of a protooncogene confers a gain of function to the gene product in
the sense that its ability to promote cell proliferation is enhanced. Mechanisms of activation of
Figure 13.5 Schematic diagram of growth factor-mediated signal transduction pathways.