Increased expression of Bcl-xL and c-Myc is associated with transformation by Abelson murine leukemia virus.
Transformation mediated by the v-Abl oncoprotein, a tyrosine kinase encoded by the Abelson murine leukemia virus, is a multi-step process requiring genetic alterations in addition to expression of v-Abl. Loss of p53 or p19ARF was previously shown to be required for Abelson murine leukemia virus transformation of primary mouse embryonic fibroblasts (MEFs). By comparing gene expression patterns in primary p53-/- MEFs acutely infected with the v-Abl retrovirus, v-Abl-transformed MEF clones, and v-Abl-transformed MEF clones treated with Abl kinase inhibitor STI 571, we have identified additional genetic alterations associated with v-Abl transformation. Bcl-xL mRNA was elevated in three of five v-Abl-transformed MEF clones. In addition, elevated expression of c-Myc mRNA, caused either by c-myc gene amplification or by enhanced signaling via STAT3, was observed in five v-Abl-transformed MEF clones. The data suggest that increases in cell survival associated with Bcl-xL and increases in cell growth associated with c-Myc facilitate the transformation process dependent on constitutive mitogenic signaling by v-Abl.
Noronha
E Jacintha
EJ
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Sterling
Karen Hinrichs
KH
Calame
Kathryn L
KL
D000011:Abelson murine leukemia virus / Q000502:physiology*; D000818:Animals; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein