Nuclear matrix as a target for hyperthermic killing of cancer cells

The nuclear matrix organizes nuclear DNA into operational domains in which DNA is undergoing replication, transcription or is inactive. The proteins o f the nuclear matrix are among the most thermal labile proteins in the cell , undergoing denaturation at temperatures as low as 43-45 degrees C, i.e. r elevant temperatures for the clinical treatment of cancer. Heat shock-induc ed protein denaturation results in the aggregation of proteins to the nucle ar matrix. Protein aggregation with the nuclear matrix is associated with t he disruption of many nuclear matrix-dependent functions (e.g. DNA replicat ion, DNA transcription, hnRNA processing, DNA repair, etc.) and cell death. Heat shock proteins are believed to bind denatured proteins and either pre vents aggregation or render aggregates more readily dissociable. While many studies suggest a role for Hsp70 in heat resistance, we have recently foun d that nuclear localization/delocalization of Hsp70 and its rate of synthes is, but not its amount, correlate with a tu mor cell's ability to prolifera te at 41.1 degrees C. These results imply that not only is the nuclear matr ix a target for the lethal effects of heat, but it also is a target for the protective, chaperoning and/or enhanced recovery effects of heat shock pro teins.