Regulation of cellular transformation by oncogenic and normal Abl kinases

Cellular transformation, the conversion of normal cells into tumorigenic cells in vitro, is characterized by immortalization, anchorage-and serum-independent growth and tumour formation in the nude mouse. Among these, anchorage-independent growth is one of the defining characteristics of transformed cells and tumour cells. Without attachment to the extracellular substrate, most normal cells cannot grow or survive, but tumour cells can proliferate. Many oncogenes and tumour suppressors are involved in regulating this process, among which is Abl tyrosine kinases. Previous work showed that v-Abl, an oncogenic variant of c-Abl kinase, induces anchorage-independent growth in the context of p53 deficiency, and a recent study by our group showed that loss of c-Abl kinase also facilitates anchorage-independent growth. The cellular context, such as a deficiency in both p53 and RB, is critical to induce anchorage independence by loss of c-Abl kinase. In this review, we discuss the mechanisms of cellular transformation by oncogenic and normal Abl kinases.