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Oncogene. 1996 Oct 3;13(7):1499-509.

p120-v-Abl expression overcomes TGF-beta1 negative regulation of c-myc transcription but not cell growth.

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Intramural Research Support Program, SAIC Frederick, Maryland 21702, USA.


Transformation of interleukin-3 dependent (IL-3) 32D-123 myeloid cells by p120-v-Abl produced the factor-independent 32D-abl cell line. In 32D-abl cells, myc expression was found to be significantly higher than in the parental cells and was correlated with increased E2F-1 protein expression and DNA binding ability. Surprisingly, in 32D-abl cells, TGF-beta1, a potent G1/S inhibitor of 32D-123 and 32D-abl cell growth, increased E2F transactivation as shown by increased c-myc promoter-CAT and GAL4-E2F-1 activity. In addition, TGF-beta1 was also found to increase E2F-1 protein levels but had no effect on steady-state retinoblastoma (RB) protein levels or phosphorylation state. In the absence of TGF-beta1, transient expression of RB in v-Abl expressing cells resulted in decreased c-myc transcription, inhibition of GAL4-E2F-1 driven transactivation and inhibition of cellular proliferation. RB and v-Abl were found to physically associate in vivo and in vitro via v-Abl's ATP binding region. In summary, these studies established that in myeloid cells: (1) v-Abl binds RB resulting in increased E2F-1-driven c-myc transcription, and (2) an alternative pathway exists for TGF-beta1-mediated growth inhibition of v-Abl-transformed cells, in which increased rather than decreased E2F-mediated c-myc transcription is observed.

[Indexed for MEDLINE]

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