PARENT SESSION
8:00 AM to 8:50 AM
Saturday, April 20, 2002
NAHS Symposium 2
NAHS Heat Shock Proteins as Therapeutic Molecules
Room: Nevada 4-5
Chair: Subjeck, John¹¹Roswell Park Cancer Institute, Buffalo, NY, Co-Chair: Carper, Stephen²²Chemistry Dept, Las Vegas, NV
Speakers: Calderwood, Stuart³; Subjeck, John¹; Henderson, Robert⁴; Carper, Stephen²³Dana Farber Cancer Institute, Boston, MA¹Roswell Park Cancer Institute, Buffalo, NY⁴, Seattle, WA²Chemistry Dept, Las Vegas, NV

(S02-1) The role of heat shock proteins in the inhibition of apoptosis.

Carper, Stephen^*,1, ¹ UNLV Cancer Institute and, Las Vegas, NV

ABSTRACT-
Heat shock proteins (hsps) can protect cells from a wide variety of stresses, especially those that induce apoptosis. My talk will primarily focus on the small heat shock protein hsp27 and it^'s role in the inhibition of apoptosis. When cells express hsps (especially hsp27 and hsp70) they become resistant to agents that induce apoptosis (i.e. chemotherapy). When this happens in cancer cells they become more difficult to eradicate. Fortunately, treatment with drugs or hormones may restore sensitivity to chemotherapeutic agents. Inhibition of apoptosis may occur in at least two distinct sites. Hsp27 can bind cytochrome c, which can inhibit the activation of caspase 9 and hence other down stream caspases. Hsp27 can also bind the protein Daxx which is a mediator of Fas-induced apoptosis. Hsp90 and hsp70 can bind to Apaf-1, one of three proteins required for the formation of the apoptosome, and thus inhibit the activation of caspase 9. When tissues that are transplanted express hsps they have a much greater survival then non-heat shocked tissue. The modulation of hsp levels can give us the ability to decrease sensitivity to apoptosis (induced by the immune response) which can be used to great therapeutic advantage.

KEYWORDS: Hsp27, Hsp70, Apoptosis, Transplantation