p53-independent role of MDM2 in TGF-beta 1 resistance

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