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

Abstract

Highlights: {yields} PD 0332991 (PD) could suppress four of five malignant rhabdoid tumor (MRT) cell lines. {yields} The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r = 0.951). {yields} p16 expression in MRT could be used to predict its sensitivity to PD. {yields} PD may be an attractive agent for patients with MRT whose tumors express low levels of p16. -- 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%, (IC{sub 50} values 0.01 to 0.6 {mu}M) 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 themore » 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.« less

Authors:
; ; ; ; ; ; ; ; ; ;  [1];  [2];  [1]
  1. Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto 602-8566 (Japan)
  2. Molecular Pharmacology, St. Jude Children's Research Hospital, 332 N. Lauderdale St. Memphis, TN 38105-2794 (United States)
Publication Date:
OSTI Identifier:
22207494
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 413; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; CELL CYCLE; CELL PROLIFERATION; CHILDREN; GLUCOSE; NEOPLASMS; PATIENTS; PHOSPHATES; RNA; SENSITIVITY; TUMOR CELLS

Citation Formats

Katsumi, Yoshiki, Iehara, Tomoko, Miyachi, Mitsuru, Yagyu, Shigeki, Tsubai-Shimizu, Satoko, Kikuchi, Ken, Tamura, Shinichi, Kuwahara, Yasumichi, Tsuchiya, Kunihiko, Kuroda, Hiroshi, Sugimoto, Tohru, Houghton, Peter J., and Hosoi, Hajime, E-mail: hhosoi@koto.kpu-m.ac.jp. Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.08.047.
Katsumi, Yoshiki, Iehara, Tomoko, Miyachi, Mitsuru, Yagyu, Shigeki, Tsubai-Shimizu, Satoko, Kikuchi, Ken, Tamura, Shinichi, Kuwahara, Yasumichi, Tsuchiya, Kunihiko, Kuroda, Hiroshi, Sugimoto, Tohru, Houghton, Peter J., & Hosoi, Hajime, E-mail: hhosoi@koto.kpu-m.ac.jp. Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression. United States. doi:10.1016/J.BBRC.2011.08.047.
Katsumi, Yoshiki, Iehara, Tomoko, Miyachi, Mitsuru, Yagyu, Shigeki, Tsubai-Shimizu, Satoko, Kikuchi, Ken, Tamura, Shinichi, Kuwahara, Yasumichi, Tsuchiya, Kunihiko, Kuroda, Hiroshi, Sugimoto, Tohru, Houghton, Peter J., and Hosoi, Hajime, E-mail: hhosoi@koto.kpu-m.ac.jp. Fri . "Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression". United States. doi:10.1016/J.BBRC.2011.08.047.
@article{osti_22207494,
title = {Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression},
author = {Katsumi, Yoshiki and Iehara, Tomoko and Miyachi, Mitsuru and Yagyu, Shigeki and Tsubai-Shimizu, Satoko and Kikuchi, Ken and Tamura, Shinichi and Kuwahara, Yasumichi and Tsuchiya, Kunihiko and Kuroda, Hiroshi and Sugimoto, Tohru and Houghton, Peter J. and Hosoi, Hajime, E-mail: hhosoi@koto.kpu-m.ac.jp},
abstractNote = {Highlights: {yields} PD 0332991 (PD) could suppress four of five malignant rhabdoid tumor (MRT) cell lines. {yields} The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r = 0.951). {yields} p16 expression in MRT could be used to predict its sensitivity to PD. {yields} PD may be an attractive agent for patients with MRT whose tumors express low levels of p16. -- 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%, (IC{sub 50} values 0.01 to 0.6 {mu}M) 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.},
doi = {10.1016/J.BBRC.2011.08.047},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 413,
place = {United States},
year = {2011},
month = {9}
}