Fig. 2.

Transformation of human MSC. (A) Schematic diagram of MSC stepwise transformation. Cell lines were named according to the number of steps or hits introduced sequentially by retroviral transduction (see Table 1). (B) Cell lines were probed by antibodies against introduced oncogenes or their downstream cellular targets. Proliferating cell nuclear antigen (PCNA) reflects cell entry in S phase after pRB inactivation by E7. (C) Anchorage-independent growth of MSC infected with empty retroviruses or combinations of different oncogenes. (D) Tumors formed in mice inoculated with 5 hits MSC (arrows), but not in those inoculated with 4 hits MSC (Left). (E) GEM profiles of five of the MSC tumors generated in mice (open circles) were compared with 96 human sarcomas (23). Multidimensional scale (MDS) shows that the tumors generated in mice clustered with human spindle cell sarcomas.