The role of the nuclear matrix in cancer chemotherapy.
The nuclear matrix is the site of many nuclear functions including transcription, replication, formation of chromatin loops, and control of DNA supercoiling. It contains various structural and functional components that represent targets for antineoplastic agents. Antimetabolites and topoisomerase II inhibitors interact specifically with matrix-associated enzymes, DNA primase, and DNA topoisomerase II, respectively. Alkylating agents and ionizing radiation interact with nuclear matrix proteins and matrix-associated DNA. Many nuclear functions, including multidrug resistance, and others which lead to cell death, have been shown to be compromised when these anticancer agents interact with the nuclear matrix.
Muenchen
H J
HJ
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0680, USA.
Pienta
K J
KJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015530:Nuclear Matrix / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure
D000970:Antineoplastic Agents; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II