Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression

Biochem Biophys Res Commun. 2011 Sep 16;413(1):62-8. doi: 10.1016/j.bbrc.2011.08.047. Epub 2011 Aug 17.


Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. MRT is characterized by inactivation of integrase interactor 1 (INI1). Cyclin-dependent kinase 4 (CDK4), which acts downstream of INI1, is required for the proliferation of MRT cells. Here we investigated the effects of PD 0332991 (PD), a potent inhibitor of CDK4, against five human MRT cell lines (MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS, KP-MRT-YM). In all of the cell lines except KP-MRT-YM, PD inhibited cell proliferation >50%, (IC(50) values 0.01 to 0.6 μM) by WST-8 assay, and induced G1-phase cell cycle arrest, as shown by flow cytometry and BrdU incorporation assay. The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r=0.951). KP-MRT-YM cells overexpress p16 and were resistant to the growth inhibitory effect of PD. Small interfering RNA against p16 significantly increased the sensitivity of KP-MRT-YM cells to PD (p<0.05). These results suggest that p16 expression in MRT could be used to predict its sensitivity to PD. PD may be an attractive agent for patients with MRT whose tumors express low levels of p16.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Child
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis*
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Drug Resistance, Neoplasm*
  • HeLa Cells
  • Humans
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology*
  • Rhabdoid Tumor / metabolism*


  • Cyclin-Dependent Kinase Inhibitor p16
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • Cyclin-Dependent Kinases
  • palbociclib