Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents.

  • Authors:
    • Y Iwadate
    • S Mochizuki
    • S Fujimoto
    • H Namba
    • S Sakiyama
    • M Tagawa
    • A Yamaura
  • View Affiliations

  • Published online on: September 1, 2000     https://doi.org/10.3892/ijo.17.3.501
  • Pages: 501-506
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Abstract

A slowly proliferating cell fraction in tumors shows reduced sensitivity to cell cycle-dependent anticancer agents. To understand the molecular basis of drug resistance observed in brain tumors, we examined the relationship between alteration of p16, a cyclin dependent kinase inhibitor whose functions are frequently lost in many human gliomas, and chemosensitivity of tumor cells to various kinds of anticancer agents. Alterations of the p16 gene that include mutation(s) and homozygous deletion as well as p16 protein expression level, were examined in 56 specimens of astrocytic tumors. Their in vitro chemosensitivities to 30 kinds of anticancer agents were analyzed with flow cytometry which detects drug-induced cell death. We found that the alterations were correlated with increased sensitivity to antimetabolite anticancer agents but not with other kinds of agents, including alkylating agents, antibiotics, topoisomerase inhibitors and antimicrotubule agents. The present results suggest that p16 plays a role in determining chemosensitivity of brain tumors, depending on pharmacological mechanisms of anticancer agents. Proper understanding of the molecular machinery which regulates the chemosensitivity may contribute to the choice of anticancer agents for individual patients.

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Sep 2000
Volume 17 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Iwadate Y, Mochizuki S, Fujimoto S, Namba H, Sakiyama S, Tagawa M and Yamaura A: Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents.. Int J Oncol 17: 501-506, 2000
APA
Iwadate, Y., Mochizuki, S., Fujimoto, S., Namba, H., Sakiyama, S., Tagawa, M., & Yamaura, A. (2000). Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents.. International Journal of Oncology, 17, 501-506. https://doi.org/10.3892/ijo.17.3.501
MLA
Iwadate, Y., Mochizuki, S., Fujimoto, S., Namba, H., Sakiyama, S., Tagawa, M., Yamaura, A."Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents.". International Journal of Oncology 17.3 (2000): 501-506.
Chicago
Iwadate, Y., Mochizuki, S., Fujimoto, S., Namba, H., Sakiyama, S., Tagawa, M., Yamaura, A."Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents.". International Journal of Oncology 17, no. 3 (2000): 501-506. https://doi.org/10.3892/ijo.17.3.501