Oncogenes growth factors expressed

Luwor RB, Lu Y, Li X, Mendelsohn J, Fan Z. The antiepidermal growth factor receptor monoclonal antibody cetuximab/C225 reduces hypoxia-inducible factor-1 alpha, leading to transcriptional inhibition of vascular endothelial growth factor expression. Oncogene 2005 24 4433-4441. 

Tsao MS, LiuN, Nicklee T, Shepherd F, Viallet J. Angiogenesis correlates with vascular endothelial growth factor expression but not with Ki-ras oncogene activation in non-small cell lung carcinoma Clin Cancer Res 1997 3 1807 1814. 

Since then, a plethora of tyrosine-phosphorylated proteins has been discovered. Originally, tyrosine phosphorylation was believed to be involved primarily in regulating cell proliferation, since many oncogene products and growth factor receptors are protein tyrosine kinases (PTKs). However, it has become clear that tyrosine phosphorylation is involved in regulating a variety of cellular processes. In fact, the nervous system contains a large variety of PTKs and protein tyrosine phosphatases (PTPs), and some of these are exclusively expressed in neuronal tissues. Figure 24-1 shows the... 

In sum, there are oncogenes that reflect every stage of this signaling pathway those that are growth factors mutant growth factor receptors that are always on signal transmission elements that are always on and inappropriate transcription factor expression. In each case, normal controls on the rate of cell division have been overcome. 

Oncogenes that express growth factors and growth factor receptors... 

The growth factor receptor(s) that are expressed by oncogenes are always active, even in the absence of the growth factor. 

Montgomery RB, Guzman J, O Rourke DM, Stahl WL. Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters beta-tubulin isotype expression. J Biol Chem 2000 275 17,358-17,363. 

Chen A, Xu J, Johnson AC. 2006. Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 25 278-287. 

Park JI, Lee MG, Cho K, Park BJ, Chae KS, Byun DS, Ryu BK, Park YK, Chi SG. 2003. Transforming growth factor-betal activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and Ras signaling pathways. Oncogene 22 4314-4332. 

It is interesting to note that expression and secretion of an aberrant HER-2 splice variant has been reported in various cell lines and tissues, which can interfere with the oncogenic HER-2 activity (Aigner et al., 2001). Expression of this truncated 100-kDa HER-2 variant encodes the extracellular domain of HER-2 and inhibits growth factor-mediated tumor cell proliferation. The exact role played by this variant during the progression of human cancer is not clear. 

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