The effects of irradiation on the expression of a tumour rejection antigen (heat shock protein gp96) in human cervical cancer.
OBJECTIVE
Studies were designed to analyse the effects of high doses of gamma-irradiation on the expression of a tumour rejection antigen (heat shock protein gp96) in human cervical carcinoma cell lines.


METHODS
The expression of heat shock protein gp96 was evaluated at the transcriptional (Northern blot) and post-transcriptional levels (Western blot) in two human cervical carcinoma cell lines following exposure to high doses of gamma-irradiation.


RESULTS
Doses of gamma-irradiation ranging from 25 to 100 Gy significantly and consistently increased the expression of heat shock protein gp96 on CaSki and HT-3 cervical cancer cells. The increase in the amount of protein was due to transcriptional up-regulation of this gene. Radiation doses unable to inhibit 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 heat shock protein gp96 mRNA in a dose-dependent manner.


CONCLUSIONS
Recently, gp96 molecules have been implicated in the presentation of endogenous and viral antigens. A number of key elements in this pathway, including major histocompatibility complex (MHC) class I molecules as well as adhesion/co-stimulation molecules such as ICAM-1, are known to be sensitive to irradiation effects. The results show that radiation can also increase the expression of other immunologically important cell molecules such as a tumour rejection antigen (heat shock protein gp96) in human cervical cancer. Such findings may partially explain the increased immunogenicity of tumour cells following irradiation and further support a role for local radiation therapy as a powerful biologic response modifier.
Santin
A D
AD
Department of Obstetrics and Gynecology, University of Arkansas, Little Rock 72205-7199, USA.
Hermonat
P L
PL
Ravaggi
A
A
Chiriva-Internati
M
M
Hiserodt
J C
JC
Batchu
R B
RB
Pecorelli
S
S
Parham
G P
GP
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000528:radiation effects; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology
D000951:Antigens, Neoplasm; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; C052646:sarcoma glycoprotein gp96 rejection antigens