| First Author | Cory S | Year | 1994 |
| Journal | Philos Trans R Soc Lond B Biol Sci | Volume | 345 |
| Issue | 1313 | Pages | 289-95 |
| PubMed ID | 7846127 | Mgi Jnum | J:21062 |
| Mgi Id | MGI:69112 | Doi | 10.1098/rstb.1994.0108 |
| Citation | Cory S, et al. (1994) Insights from transgenic mice regarding the role of bcl-2 in normal and neoplastic lymphoid cells. Philos Trans R Soc Lond B Biol Sci 345(1313):289-95 |
| abstractText | The bcl-2 gene was first discovered by molecular analysis of the 14;18 chromosome translocation which is the hallmark of most cases of human follicular lymphoma. To date, it is unique among proto-oncogenes because, rather than promoting cell proliferation, it fosters cell survival. This review summarizes the impact of constitutive bcl-2 expression on the development and function of lymphocytes as well as their malignant transformation. Expression of a bcl-2 transgene in the B lymphoid compartment profoundly perturbed homeostasis and, depending on the genetic background, predisposed to a severe autoimmune disease resembling human systemic lupus erythematosus. T lymphoid cells from bcl-2 transgenic mice were remarkably resistant to diverse cytotoxic agents. Nevertheless, T lymphoid homeostasis was unaffected and tolerance to self was maintained. Expression of high levels of Bcl-2 facilitated the development of B lymphoid tumours but at relatively low frequency and with long latency. Co-expression of myc and bcl-2, on the other hand, promoted the rapid onset of novel tumours which appeared to derive from a lympho-myeloid stem or progenitor cell. Introduction of the bcl-2 transgene into scid mice facilitated the survival and differentiation of pro-B but not pro-T cells, suggesting that a function necessary to supplement or complement the action of Bcl-2 is expressed later in the T than the B lineage. Crosses of the bcl-2 transgenic mice with p53-/- mice have addressed whether loss of p53 function and gain of bcl-2 function are synergistic for lymphoid cell survival. |
