Survivin as a radioresistance factor in pancreatic cancer.
We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy.
Asanuma
K
K
Department of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8543, Japan.
Moriai
R
R
Yajima
T
T
Yagihashi
A
A
Yamada
M
M
Kobayashi
D
D
Watanabe
N
N
D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000528:radiation effects; D011836:Radiation Tolerance / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014965:X-Rays
C107489:BIRC5 protein, human; D061945:Caspase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D000077022:Survivin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases