Cell Transformation proto-oncogenes

All normal cells have proto-oncogenes in their nucleus. There are at least 70 different proto-oncogenes in the cell. Such genes are considered to play an important role in the regulation of cell growth and differentiation. However, they can be activated into oncogenes, which then induce neoplastic transformation. 

A unifying theme of the role of oncogene function in cell transformation is that the expression of the proto-oncogenes is normally tightly... 

Proto-oncogenes found in mammalian cells have homology to genes found in transforming retroviruses. Well more than 60 proto-oncogenes have been recog-... 

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. 

Hydrogen peroxide transformed mouse myeloid progenitor cells (FDC-Pl) from interleukin-3 dependence to factor independence, but only at cytotoxic concentrations (> 12/5 pmol/L). Such a transformation was not induced by non-specific insults to the cells, such as sodium fluoride or heat shock treatment. The transformed cells produced tumours when injected into pre-irradiated mice (Crawford Greenberger, 1991). Hydrogen peroxide (10 pmol/L) induced overexpression of the proto-oncogene c-jun in hamster tracheal epithelial (HTE) cells c-jun overexpression led to proliferation and increased growth rate, as well as increased anchorage-independence of HTE cells (Timblin et al., 1995). 

Since many cellular oncogenes were originally identified in transforming retroviruses, and since some retroviruses cause rapid malignant transformation in animals, notably chicken, it seemed for a while that most human cancers are caused by infection with retroviruses. But that is not the case. The number of human cancers which originate from retroviral infections is actually rather small (Table 15.2). In many cases, proto-oncogenes can become oncogenes by mutation or overexpression in human cells, without retroviral assistance. 

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