UC Berkeley

Apparently, science has fought a long war on cancer with a myriad of efforts. Nonetheless cancer is still one of the leading causes of death, and our understanding of cancer remains very narrow. Many studies have recognized that one of the hallmark features of cancer is the complex involvement of many cellular components and events throughout cancer development.

In 1970, Abelson-Murine Leukemia Virus (A-MuLV) was accidentally discovered as a replication-defective mutant retrovirus that causes acute leukemia in mice. A-MuLV can infect mouse bone marrow, and generate so-called Abelson transformed cell lines. However, A-MuLV infected cells exhibit two distinct stages of transformation with stringent clonal selection during the transformation process. This suggests that in addition to expression of the viral oncogene v-Abl, cellular factors also play an important role in the transformation process.

Here, we studied this v-Abl transformation system to ask some questions about how cellular factors are involved in leukemic transformation. 1) Are there a unique subset of cell populations susceptible to v-Abl transformation? With bone marrow fractionation experiments, we confirmed that pro-B cells are the major target cells of v-Abl transformation. 2) In which stages of the process is tumor suppressor p53 involved in the transformation? p53 knock-down studies clearly validated that p53 is also involved in early v-Abl transformation, as well as later stages. 3) Are there any other cellular factors important in v-Abl transformation? A loss-of-function screen identified Dpf2, a zinc finger transcription factor, as a protein that can affect v-Abl transformation in a p53-dependent manner.

In the meanwhile, we have developed a 96 well round-bottom plate assay that can measure initial v-Abl transformation frequency reliably and accurately. Also we have implemented a sequential infection method, which could provide a good platform to allow genetic manipulation of cells during the transformation process. These assays should facilitate answering many more questions about the v-Abl transformation process.