T antigens' role in polyomavirus transformation: c-myc but not c-fos or c-jun expression is a target for middle T.

Rameh LE, Armelin MC
Oncogene. 1991 6 (6): 1049-56

PMID: 1648700

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.

MeSH Terms (17)

Animals Antigens, Polyomavirus Transforming Cell Line Cell Transformation, Viral DNA-Binding Proteins Fibroblasts Gene Expression Mice Mice, Inbred BALB C Polyomavirus Proto-Oncogene Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Proto-Oncogene Proteins c-myc RNA, Messenger Transcription Factors Transfection

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