Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells.
A common feature of follicular lymphoma, the most prevalent haematological malignancy in humans, is a chromosome translocation (t(14;18] that has coupled the immunoglobulin heavy chain locus to a chromosome 18 gene denoted bcl-2. By analogy with the translocated c-myc oncogene in other B-lymphoid tumours bcl-2 is a candidate oncogene, but no biological effects of bcl-2 have yet been reported. To test whether bcl-2 influences the growth of haematopoietic cells, either alone or together with a deregulated c-myc gene, we have introduced a human bcl-2 complementary DNA using a retroviral vector into bone marrow cells from either normal or E mu-myc transgenic mice, in which B-lineage cells constitutively express the c-myc gene. Bcl-2 cooperated with c-myc to promote proliferation of B-cell precursors, some of which became tumorigenic. To determine how bcl-2 expression impinges on growth factor requirements, the gene was introduced into a lymphoid and a myeloid cell line that require interleukin 3 (IL-3). In the absence of IL-3, bcl-2 promoted the survival of the infected cells but they persisted in a G0 state, rather than proliferating. These results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.
Vaux
D L
DL
Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
Cory
S
S
Adams
J M
JM
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D005434:Flow Cytometry; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007377:Interleukin-3 / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes; D011519:Proto-Oncogenes; D012190:Retroviridae / Q000235:genetics; D014162:Transfection
D007377:Interleukin-3