Bcl-2 and c-Myc co-operate in the Epstein-Barr virus-immortalised human B-cell line GM607 but do not confer tumourigenicity

Tomlin, Jennifer L., Guinn, Barbara-Ann, Penn, Linda Z. and Berinstein, Neil L. (2005) Bcl-2 and c-Myc co-operate in the Epstein-Barr virus-immortalised human B-cell line GM607 but do not confer tumourigenicity. Leukemia and Lymphoma, 46 (4), 581-592. (doi:10.1080/10428190400019867).

Abstract

Eighty-five percent of follicular lymphomas (FL) possess a characteristic t(14;18) translocation that results in the deregulated expression of the proto-oncogene BCL-2. BCL-2 overexpression alone is insufficient for full cellular transformation and at least one other genetic event is believed to be necessary for FL development. Deregulated c-Myc expression has previously been shown to co-operate with Bcl-2 to transform murine fibroblast cell lines and lead to tumor development in mice. We have developed a human model system to study early transformation in lymphoid cells using immortalised lymphoblastoid cells. We sequentially introduced BCL-2 and c-MYC, two proto-oncogenes known to be involved in the transformation of B-cells into EBV immortalised human B cells. We show that the c-Myc and Bcl-2 overexpression, together with EBV immortalization were insufficient to cause full cellular transformation as measured by cell proliferation rates, soft agar and tumourigenicity assays. These results show that more than three genetic hits (EBV infection, BCL-2 and c-MYC overexpression) were required for the full cellular transformation of human lymphoblastoid cells. However, subtle changes in cellular proliferation and sensitivity to apoptosis were documented, at non-limiting dilutions. These changes may confer a susceptibility to the modified cells such that they are more susceptible to the acquisition of additional genetic changes and evolve towards a fully transformed state. In addition, the model system developed may be suitable for the identification of further known and novel oncogenic events involved in the full transformation of B-cells

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