The functional basis of c-myc and bcl-2 complementation during multistep lymphomagenesis in vivo.
Oncogenes are known to be deregulated by chromosomal translocations occurring at high frequency in specific malignancies. Among the most well characterized of these are c-myc, associated with the t(8;14) in Burkitt's lymphomas, and bcl-2, associated with the t(14;18) in follicular lymphomas. In addition to their role in regulating rates of proliferation, it is known that oncogenes and tumor suppressor genes can also regulate rates of apoptotic cell death. The contribution of c-myc and bcl-2 to the regulation of cell death during lymphomagenesis in vivo is assessed using bcl-2-Ig and emu-myc trangenic mice and bcl-2/myc hybrid transgenic mice. Translocations between the endogenous c-myc gene and immunoglobulin loci, e.g., t(12;15), are common in lymphomas arising in the bcl-2-Ig mice. Furthermore, bcl-2/c-myc double transgenic mice exhibit accelerated lymphomagenesis, indicating cooperation between these two oncogenes. Genetic complementation of c-myc and bcl-2 during lymphomagenesis resulted from the suppression of c-myc-associated apoptosis. Other genes are likely involved in regulating cell death during multistep lymphomagenesis.
Marin
M C
MC
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Hsu
B
B
Stephens
L C
LC
Brisbay
S
S
McDonnell
T J
TJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000528:radiation effects; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D005816:Genetic Complementation Test; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2