Human Biochemistry Volume 2 - Murray R. 1993

Special Topics
Cancer, Oncogenes, Growth Factors
Polypeptide Growth Factors - Growth Factors and Oncogenes

As is now known, the products of A number of oncogenes are either growth factors or their "truncated" receptors (Table 57.6).

The platelet-derived growth factor B-chain consists of 109 Amino Acids. It is highly probable that the B-chain is biologically active as a homodimer without the involvement of the A-chain. It has been shown that the v-sis Gene encodes 100 of the 109 amino acids of the B-chain; this discovery revealed a direct link between oncogenes and growth factors. It can be hypothesized that autocrine regulation mediated by this growth factor plays a crucial role in Cell transformation by the v-sis gene. Indeed, many cultured tumor Cells secrete growth factors into their environment while simultaneously expressing receptors for these molecules.

Analysis of the Introduction/19.html">Primary Structure of v-erb-B revealed that this gene determines The formation of a truncated form of the EGFR receptor, lacking a large portion of the extracellular domain while retaining protein kinase activity. It has been suggested that the truncated EGFR form encoded by v-erb-B may be active inside The Cell, mimicking a receptor bound to an endogenous growth factor. As in the case of autocrine stimulation by platelet-derived growth factor, this can lead to a continuous mitogenic "signal" driving cells toward a transformed state.

Transforming growth factor-beta (TGF-β) was initially considered a positive (stimulating) factor because its addition to fibroblast cultures caused them to behave like transformed cells. It is now established that TGF-β inhibits the growth of most cell types (with the exception of fibroblasts). It also suppresses the growth of monkey Kidney cells that synthesize it. TGF-β can activate the sis gene in fibroblasts. The Mechanism of growth inhibition in other cells remains unclear. Evidence suggests that certain genes encode products that slow down cell growth; furthermore, there are genes that suppress tumor development. Thus, cell growth control is a complex process that can be regulated by both stimulatory and inhibitory factors.