title: Gene expression profiling of breast, prostate, and glioma cells following single versus fractionated doses of radiation.
abstract: Studies were conducted to determine whether gene expression profiles following a single dose of radiation would yield equivalent profiles following fractionated radiation in different tumor cell lines. MCF7 (breast), DU145 (prostate), and SF539 (gliosarcoma) cells were exposed to a total radiation dose of 10 Gy administered as a single dose (SD) or by daily multifractions (MF) of 5 x 2 Gy. Following radiation treatment, mRNA was isolated at 1, 4, 10, and 24 h and processed for cDNA microarray analysis. To determine the influence of the tumor microenvironment on gene expression, one cell type (DU145) was evaluated growing as a solid tumor in athymic nude mice for both radiation protocols. Unsupervised hierarchical cluster map analysis showed significant differences in gene expression profiles between SD and MF treatments for cells treated in vitro, with MF yielding a more robust induction compared with SD. Several genes were uniquely up-regulated by MF treatment, including multiple IFN-related genes (STAT1, G1P2, OAS1, OAS3, G1P3, IFITM1) and TGF-beta-associated genes (EGR1, VEGF, THBS1, and TGFB2). DU145 cells grown in vivo exhibited a completely different set of genes induced by both SD and MF compared with the same cells exposed in vitro. The results of the study clearly show distinct differences in the molecular response of cells between SD and MF radiation exposures and show that the tumor microenvironment can significantly influence the pattern of gene expression after radiation exposures.
authors: Radiation Biology, Center for Cancer Research, National Cancer Institute/NIH, Bethesda, MD 20892, USA.
authors: Mong-Hsun
authors: MH
authors: Tsai
authors: John A
authors: JA
authors: Cook
authors: Gadisetti V R
authors: GV
authors: Chandramouli
authors: William
authors: W
authors: DeGraff
authors: Hailing
authors: H
authors: Yan
authors: Shuping
authors: S
authors: Zhao
authors: C Norman
authors: CN
authors: Coleman
authors: James B
authors: JB
authors: Mitchell
authors: Eric Y
authors: EY
authors: Chuang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019583:Dose Fractionation, Radiation; D005260:Female; D015870:Gene Expression / Q000528:radiation effects; D020869:Gene Expression Profiling; D016158:Genes, p53 / Q000528:radiation effects; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007372:Interferons / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D016212:Transforming Growth Factor beta; D007372:Interferons