title: IGFBP3 and BAG1 enhance radiation-induced apoptosis in squamous esophageal cancer cells.
abstract: Identification of reliable markers of radiosensitivity and the key molecules that enhance the susceptibility of esophageal cancer cells to anticancer treatments would be highly desirable. To identify molecules that confer radiosensitivity to esophageal squamous carcinoma cells, we assessed the radiosensitivities of the TE-5, TE-9 and TE-12 cloneA1 cell lines. TE-12 cloneA1 cells showed significantly greater susceptibility to radiotherapy at 5 and 10Gy than either TE-5 or TE-9 cells. Consistent with that finding, 24h after irradiation (5Gy), TE-12 cloneA1 cells showed higher levels of caspase 3/7 activity than TE-5 or TE-9 cells. When we used DNA microarrays to compare the gene expression profiles of TE-5 and TE-12 cloneA1 cells, we found that the mRNA and protein expression of insulin-like growth factor binding protein 3 (IGFBP3) and Bcl-2-associated athanogene 1 (BAG1) was five or more times higher in TE-12 cloneA1 cells than TE-5 cells. Conversely, knocking down expression of IGFBP3 and BAG1 mRNA in TE-12 cloneA1 cells using small interfering RNA (siRNA) significantly reduced radiosensitivity. These data suggest that IGFBP3 and BAG1 may be key markers of radiosensitivity that enhance the susceptibility of squamous cell esophageal cancer to radiotherapy. IGFBP3 and BAG1 may thus be useful targets for improved and more individualized treatments for patients with esophageal squamous cell carcinoma.
authors.affiliation: Department of Surgery, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yoshino
authors.forename: Satoru
authors.initials: S
authors.lastname: Motoyama
authors.forename: Souichi
authors.initials: S
authors.lastname: Koyota
authors.forename: Kaori
authors.initials: K
authors.lastname: Shibuya
authors.forename: Shuetsu
authors.initials: S
authors.lastname: Usami
authors.forename: Kiyotomi
authors.initials: K
authors.lastname: Maruyama
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Minamiya
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Ogawa
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000532:radiotherapy*; D055785:Gene Knockdown Techniques; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D014157:Transcription Factors