PTTG1 attenuates drug-induced cellular senescence.

ABSTRACT: As PTTG1 (pituitary tumor transforming gene) abundance correlates with adverse outcomes in cancer treatment, we determined mechanisms underlying this observation by assessing the role of PTTG1 in regulating cell response to anti-neoplastic drugs. HCT116 cells devoid of PTTG1 (PTTG1(-/-)) exhibited enhanced drug sensitivity as assessed by measuring BrdU incorporation in vitro. Apoptosis, mitosis catastrophe or DNA damage were not detected, but features of senescence were observed using low doses of doxorubicin and TSA. The number of drug-induced PTTG1(-/-) senescent cells increased ∼4 fold as compared to WT PTTG1-replete cells (p<0.001). p21, an important regulator of cell senescence, was induced ∼3 fold in HCT116 PTTG1(-/-) cells upon doxorubicin or Trichostatin A treatment. Binding of Sp1

SUBMITTER: Tong Y 

PROVIDER: S-EPMC3157437 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature