Coordinate late expression of trefoil peptide genes (pS2/TFF1 and ITF/TFF3) in human breast, colon, and gastric tumor cells exposed to X-rays.
The trefoil factors (TFFs) are pleiotropic factors involved in organization and homeostasis of the gastrointestinal tract, estrogen responsiveness, inflammatory disorders, and carcinogenesis. In an earlier study using cDNA array technologies to identify new genes expressed in irradiated cell survivors, we isolated a cDNA clone corresponding to the reported human TFF1 gene (E. K. Balcer-Kubiczek et al., Int. J. Radiat. Biol., 75: 529-541, 1999). To determine whether expression of other TFFs is altered by ionizing radiation, we quantified changes in expression of TFF3 as well as TFF1 in RNA samples obtained from irradiated and control human tumor breast, colon, and gastric tumor cells and examined expression kinetics up to 2 weeks after irradiation. X-ray-induced TFF1 and TFF3 expression profiles were compared with those induced by hydrogen peroxide (H2O2) or 17beta-estradiol (ES). The results revealed that TFF1 and TFF3 mRNA are coinduced by X-irradiation in a subset of the lines, but substantial heterogeneity in their responses was observed in cells derived from a single cell type. TFF1 and TFF3 transcriptional response to X-irradiation differed from that to H2O2 or ES in the timing of their induction as well as tissue-type dependence, i.e., their induction pattern after X-irradiation was late and sustained, whereas their induction by H2O2 or ES was early and transient. TFF1 mRNA, protein production in the cytoplasm, and secretion in the culture supernatant were coordinately regulated after X-irradiation. There was no requirement for TP53 in this induction. These results demonstrate the existence of a novel class of radiation-responsive genes that might be involved in bystander effects.
Balcer-Kubiczek
Elizabeth K
EK
Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ekubicze@umaryland.edu
Harrison
George H
GH
Xu
Jing-Fan
JF
Gutierrez
Peter L
PL
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003114:Colony-Forming Units Assay; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression / Q000528:radiation effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009077:Mucins; D009124:Muscle Proteins; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D010455:Peptides; D010637:Phenolsulfonphthalein / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D025521:Tumor Suppressor Proteins
D009077:Mucins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017382:Reactive Oxygen Species; C051838:TFF1 protein, human; C082495:TFF3 protein, human; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D004958:Estradiol; D006861:Hydrogen Peroxide; D010637:Phenolsulfonphthalein