Gene expression profile in human late radiation enteritis obtained by high-density cDNA array hybridization.
Late radiation enteritis is a sequela of radiation therapy to the abdomen. The pathogenic process is poorly understood at the molecular level. cDNA array analysis was used to provide new insights into the pathogenesis of this disorder. Gene profiles of six samples of fibrotic bowel tissue from patients with radiation enteritis and six healthy bowel tissue samples from patients without radiation enteritis were compared using membrane-based arrays containing 1314 cDNAs. Results were confirmed with real-time RT-PCR and Western blot analysis. Array analysis identified many differentially expressed genes involved in fibrosis, stress response, inflammation, cell adhesion, intracellular and nuclear signaling, and metabolic pathways. Increased expression of genes coding for proteins involved in the composition and remodeling of the extracellular matrix, along with altered expression of genes involved in cell- to-cell and cell-to-matrix interactions, were observed mainly in radiation enteritis samples. Stress, inflammatory responses, and antioxidant metabolism were altered in radiation enteritis as were genes coding for recruitment of lymphocytes and macrophages. The Rho/HSP27 (HSPB1)/zyxin pathway, involved in tissue contraction and myofibroblast transdifferentiation, was also altered in radiation enteritis, suggesting that this pathway could be related to the fibrogenic process. Our results provide a global and integrated view of the alteration of gene expression associated with radiation enteritis. They suggest that radiation enteritis is a dynamic process involving constant remodeling of each structural component of the intestinal tissue, i.e. the mucosa, the mesenchyme, and blood vessels. Functional studies will be necessary to validate the present results.
Laboratoire UPRES EA 27-10 Radiosensibilité des tumeurs et tissus sains, Institut Gustave Roussy/Institut de Radioprotection et de Sûreté Nucléaire, Villejuif, France. vozenin@igr.fr
Marie-Catherine
MC
Vozenin-Brotons
Fabien
F
Milliat
Christine
C
Linard
Carine
C
Strup
Agnès
A
François
Jean-Christophe
JC
Sabourin
Philippe
P
Lasser
Antoine
A
Lusinchi
Eric
E
Deutsch
Theo
T
Girinsky
Jocelyne
J
Aigueperse
Jean
J
Bourhis
Denis
D
Mathé
D000328:Adult; D000368:Aged; D004751:Enteritis / Q000209:etiology* / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D007082:Ileum / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000532:radiotherapy; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011831:Radiation Genetics / Q000379:methods; D011832:Radiation Injuries / Q000209:etiology* / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D013997:Time Factors