THE EFFECTS OF IRRADIATION ON THE EXPRESSION OF A TUMOR REJECTION ANTIGEN (HEAT-SHOCK-PROTEIN GP96) IN HUMAN CERVICAL-CANCER

Purpose: Studies were designed to analyse the effects of high doses of gamma-irradiation on the expression of a tumour rejection antigen (he al shock protein gp96) in human cervical carcinoma cell lines. Materia ls and methods: The expression of heat shock protein gp96 was evaluate d at the transcriptional (Northern blot) and posttranscriptional level s (Western blot) in two human cervical carcinoma cell lines following exposure to high doses of gamma-irradiation Results: Doses of gamma-ir radiation ranging from 25 to 100 Gy significantly and consistently inc reased the expression of heat shock protein gp96 on CaSki and HT-3 cer vical cancer cells. The increase in the amount of protein was due to t ranscriptional up-regulation of this gene. Radiation doses unable to i nhibit completely cell replication in the totality of tumour cells (i. e. 25 Gy), as well as higher (fully lethal) doses of irradiation (i.e. 50 to 100 Gy), were shown to up-regulate significantly the expression of heal shock protein gp96 mRNA in a dose-dependent manner. Conclusio ns: Recently, gp96 molecules have been implicated in the presentation of endogenous and viral antigens. A number of key elements in this pat hway, including major histocompatibility complex (MHC) class I molecul es as well as adhesion/costimulation molecules such as ICAM-1, are kno wn to be sensitive to irradiation effects. The results show that radia tion can also increase the expression of other immunologically importa nt cell molecules such as a tumour rejection antigen (heat shock prote in gp96) in human cervical cancer. Such findings may partially explain the increased immunogenicity of tumour cells following irradiation an d further support a role for local radiation therapy as a powerful bio logic response modifier.