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

Yoshiki Katsumi, Tomoko Iehara, Mitsuru Miyachi, Shigeki Yagyu, Satoko Tsubai-Shimizu, Ken Kikuchi, Shinichi Tamura, Yasumichi Kuwahara, Kunihiko Tsuchiya, Hiroshi Kuroda, Tohru Sugimoto, Peter J. Houghton, Hajime Hosoi

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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%, (IC50 values 0.01 to 0.6μM) 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.

Original languageEnglish (US)
Pages (from-to)62-68
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume413
Issue number1
DOIs
StatePublished - Sep 16 2011
Externally publishedYes

Keywords

  • CDK4
  • INI1
  • P16
  • PD 0332991
  • Rhabdoid tumor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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