Gene expression profiling of breast, prostate, and glioma cells following single versus fractionated doses of radiation
Journal
Cancer Research
Journal Volume
67
Journal Issue
8
Pages
3845-3852
Date Issued
2007
Author(s)
Cook, John A.
ramouli, Gadisetti V.R.
DeGraff, William
Yan, Hailing
Zhao, Shuping
Coleman, C. Norman
Mitchell, James B.
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, 0AS3, G1P3, IFITM1) and TGF-β-associated genes (EGB1, 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. ?2007 American Association for Cancer Research.
SDGs
Other Subjects
complementary DNA; messenger RNA; STAT1 protein; vasculotropin; article; breast adenocarcinoma; cancer survival; cell cycle; cell differentiation; gene control; gene expression; glioma cell; human; human cell; in vitro study; in vivo study; microarray analysis; priority journal; prostate carcinoma; radiation dose; radiation exposure; RNA isolation; solid tumor; tumor growth; upregulation; Animals; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cluster Analysis; Dose Fractionation; Female; Gene Expression; Gene Expression Profiling; Genes, p53; Glioma; Humans; Interferons; Male; Mice; Mice, Nude; Neoplasm Transplantation; Oligonucleotide Array Sequence Analysis; Prostatic Neoplasms; Transforming Growth Factor beta; Transplantation, Heterologous; Up-Regulation
Type
journal article
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