title: S100A4 mRNA expression level is a predictor of radioresistance of pancreatic cancer cells.
abstract: Improving poor outcomes in patients with pancreatic cancer requires a greater understanding of the biological mechanisms contributing to radioresistance. We, therefore, sought to identify genes involved in the radioresistance of pancreatic cancer cells. Two pancreatic cancer cell lines, CFPAC-1 and Capan-1, were repeatedly exposed to radiation, establishing two radioresistant cell lines. Gene expression profiling using cDNA microarrays was performed to identify genes responsible for radioresistance. The levels of expression of mRNAs encoded by selected genes and their correlation with radiation dose resulting in 50% survival rate were analyzed in pancreatic cancer cell lines. The radiation dose resulting in a 50% survival rate was significantly higher in irradiated (IR) compared to parental CFPAC-1 cells (8.31 ± 0.85 Gy vs. 2.14 ± 0.04 Gy, P<0.0001), but was lower in IR compared with parental Capan-1 cells (2.66 ± 0.24 Gy vs. 2.25 ± 0.03 Gy, P=0.04). cDNA microarray analysis identified 4 genes, including S100 calcium binding protein A4 (S100A4), overexpressed and 23 genes underexpressed in the IR compared with the parental cell lines. The levels of S100A4 mRNA expression were correlated with radiation dose resulting in a 50% survival rate (Pearson's test, R2=0.81, P=0.0025). S100A4 mRNA expression may predict radioresistance of pancreatic cancer cells and may play an important role in the poor response of pancreatic cancer cells to radiation therapy.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kozono
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.forename: Daiki
authors.initials: D
authors.lastname: Eguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000235:genetics*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human