p53-independent role of MDM2 in TGF-beta1 resistance.

نویسندگان

  • P Sun
  • P Dong
  • K Dai
  • G J Hannon
  • D Beach
چکیده

Transforming growth factor-beta (TGF-beta) inhibits cell proliferation, and acquisition of TGF-beta resistance has been linked to tumorigenesis. A genetic screen was performed to identify complementary DNAs that abrogated TGF-beta sensitivity in mink lung epithelial cells. Ectopic expression of murine double minute 2 rescued TGF-beta-induced growth arrest in a p53-independent manner by interference with retinoblastoma susceptibility gene product (Rb)/E2F function. In human breast tumor cells, increased MDM2 expression levels correlated with TGF-beta resistance. Thus, MDM2 may confer TGF-beta resistance in a subset of tumors and may promote tumorigenesis by interference with two independent tumor suppressors, p53 and Rb.

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عنوان ژورنال:
  • Science

دوره 282 5397  شماره 

صفحات  -

تاریخ انتشار 1998