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Science 18 December 1998:
Vol. 282. no. 5397, pp. 2270 - 2272
DOI: 10.1126/science.282.5397.2270
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Reports

p53-Independent Role of MDM2 in TGF-beta 1 Resistance

Peiqing Sun, Ping Dong, Kang Dai, * Gregory J. Hannon, David Beach dagger

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.

P. Sun, P. Dong, K. Dai, G. J. Hannon, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. D. Beach, the Institute of Child Health, 30 Guilford Street, London WC1N, UK.
*   Present address: Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.

dagger    To whom correspondence should be addressed. E-mail: d.beach{at}ich.ucl.ac.uk

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Science. ISSN 0036-8075 (print), 1095-9203 (online)