Cell proliferation: oncogenes

Takada Y, Bhardwaj A, Potdar P, Aggarwal BB. 2004. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin Dl, and abrogation of tumor cell proliferation. Oncogene 23 9247-9258. 

Aigner, A., Juhl, H., Malerczyk, C., Tkybusch, A., Benz, C. C., and Czubayko, F. 2001. Expression of a truncated 100 kDa HER2 splice variant acts as an endogenous inhibitor of tumor cell proliferation. Oncogene 20 2101-2111. 

M.A. Shupnik, Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways implications for cell proliferation, Oncogene 2004, 23, 7979-7989. 

Normal cellular gene, usually concerned with the regulation of cell proliferation that can be converted to a cancer promoting oncogene by mutation. 

Targeted cancer therapy refers to anticancer treatments that selectively interfere with molecules ( oncogenes and antioncogenes) considered to be important in neoplastic transformation, cell proliferation, invasion... 

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... 

Kim, H. A., Rosenbaum, T., Marchionni, M. A., Ratner, N. and DeClue, J. E. Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes. Oncogene 11 325-335,1995. 

Looked at another way, the four major carcinogenic mechanisms are DNA damage, cell toxicity, cell proliferation and oncogene activation. Any effective program to identify those drags which have the potential to cause or increase the incidence of neoplasia in humans must effectively screen for these mechanisms (Kitchin, 1999). 

NUCLEOLIN AS A PROTO-ONCOGENE THAT STIMULATES CELL PROLIFERATION... 

Tumor cells differ from normal cells in one dramatic way they have lost the susceptibility to normal controls on cell proliferation. It should not surprise us then to learn that tumor suppressor genes and proto-oncogenes fall into one of three key categories. First, some oncogenic mutations directly affect cell proliferation. Second, other oncogenic mutations lead to loss of cell cycle control. Third, still other oncogenic mutations lead to genomic instability. 

Finally, inappropriate expression of nuclear transcription factors can lead to cell transformation. For example, the products of he,fos and myc proto-oncogenes are transcription factors that regulate the expression of proteins that promote progression through the cell cycle. Levels of the Fos and Myc proteins are tightly regulated in normal cells. Uncontrolled expression of these proteins leads to cell proliferation. 

DNA-binding proteins. A whole series of oncogenes code for transcription factors. Particularly important for cell proliferation are myc, as well as fos and jun. The protein products of the latter two genes form the transcription factor AP-1 as a heterodimer (see p. 244). 

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