Induction of PBP74/mortalin/Grp75, a member of the hsp70 family, by low doses of ionizing radiation: a possible role in induced radioresistance.
The identification of genes whose expression is altered following exposure to a low dose of ionizing radiation (IR) is an important step in understanding the phenomenon of the adaptive response. Using the differential mRNA display method we have identified a gene whose expression is up-regulated following exposure to 0.25 Gy IR. Partial DNA sequence and restriction endonuclease analysis of this gene showed that it is identical to the gene encoding for the human peptide-binding protein 74 (PBP74/mortalin/Grp75), a member of the heat shock 70 protein family. Time-course measurement of the PBP74/mortalin/Grp75 mRNA showed that its level was elevated after a lag of at least 15 min. The maximum induction appears to be at 30 min following gamma-irradiation and there is then a steady decline to control levels within 5 h in the HT29 cell line. On the other hand, the level of the PBP74/mortalin/Grp75 mRNA in the human breast adenocarcinoma cell line MCF-7 is consistently elevated after gamma-irradiation for up to 6 h post-irradiation. Furthermore, a cell line that does not demonstrate the induced radioresistance phenomenon (SW48) shows no induction of the PBP74/mortalin/Grp75 mRNA in contrast with HT29 or MCF-7. Treatment of the HT29 cells with antisense oligonucleotide directed towards the initiation codon of PBP74 sensitized cells to ionizing radiation.
Sadekova
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Department of Oncology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Lehnert
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Chow
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D001483:Base Sequence; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011836:Radiation Tolerance
D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C080352:mortalin