T antigens' role in polyomavirus transformation: c-myc but not c-fos or c-jun expression is a target for middle T.
Polyoma virus (Py) causes neoplastic transformation in vitro and multiple tumors in vivo. The role played by large and middle T antigens (LT, MT) and their mechanisms of action are focused here. Py-transformed Balb-3T3 cells become independent of platelet-derived growth factor (PDGF) for growth. JE, c-fos, c-jun and c-myc are 'immediate early' genes induced in response to PDGF. To test whether these cellular genes play a role in malignant transformation by Py, we generated a number of transfectant cell lines overexpressing LT, MT or both. Characterization of these cell lines revealed that: (a) MT but not LT causes morphological transformation, ability to grow in agarose suspension; (b) cooperation between LT and MT is evident in vitro, however, high and simultaneous LT and MT expression does not warrant tumorigenic potential; (c) MT expression does not correlate with tumorigenic potential but alters the probability of eliciting tumors; (d) JE and c-myc (but not c-fos or c-jun) are constitutively expressed in MT transfectants. MT induction is followed by c-myc induction 1.5 h later. We conclude that some of the 'immediate-early' genes may play pivotal roles in Py transformation.
Rameh
L E
LE
Universidade de São Paulo, Instituto de Quimica, Brasil.
Armelin
M C
MC
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011120:Polyomavirus / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors