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

Iwadate,Y; Mochizuki,S; Fujimoto,S; Namba,H; Sakiyama,S; Tagawa,M; Yamaura,A

doi:10.3892/ijo.17.3.501

Sep 2000 Volume 17 Issue 3

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Sep 2000 Volume 17 Issue 3

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Article

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 / Copyright

Affiliations: Department of Neurosurgery, Chiba University School of Medicine, Chuou-ku, Japan.
Pages: 501-506
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Published online on: September 1, 2000

https://doi.org/10.3892/ijo.17.3.501
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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.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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