title: A novel radioresistant mechanism of galectin-1 mediated by H-Ras-dependent pathways in cervical cancer cells.
abstract: Galectin-1 is a lectin recognized by galactoside-containing glycoproteins, and is involved in cancer progression and metastasis. The role of galectin-1 in radiosensitivity has not previously been investigated. Therefore, this study tests whether galectin-1 is involved in the radiosensitivity mediated by the H-Ras signaling pathway using cervical carcinoma cell lines. A knockdown of galectin-1 expression in HeLa cells decreased clonogenic survival following irradiation. The clonogenic survival increased in both HeLa and C33A cells with galectin-1 overexpression. The overexpression or knockdown of galectin-1 did not alter radiosensitivity, whereas H-Ras was silenced in both cell lines. Whereas K-Ras was knocked down, galectin-1 restored the radiosensitivity in HeLa cells and C33A cells. The knockdown of galectin-1 increased the high-dose radiation-induced cell death of HeLa cells transfected by constitutively active H-Ras. The knockdown of galectin-1 inhibited the radiation-induced phosphorylation of Raf-1 and ERK in HeLa cells. Overexpression of galectin-1 enhanced the phosphorylation of Raf-1 and ERK in C33A cells following irradiation. Galectin-1 decreased the DNA damage detected using comet assay and γ-H2AX in both cells following irradiation. These findings suggest that galectin-1 mediates radioresistance through the H-Ras-dependent pathway involved in DNA damage repair.
authors.affiliation: Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: E-Y
authors.initials: EY
authors.lastname: Huang
authors.forename: Y-F
authors.initials: YF
authors.lastname: Chen
authors.forename: Y-M
authors.initials: YM
authors.lastname: Chen
authors.forename: I-H
authors.initials: IH
authors.lastname: Lin
authors.forename: C-C
authors.initials: CC
authors.lastname: Wang
authors.forename: W-H
authors.initials: WH
authors.lastname: Su
authors.forename: P-C
authors.initials: PC
authors.lastname: Chuang
authors.forename: K-D
authors.initials: KD
authors.lastname: Yang
mesh_terms: D020552:Comet Assay; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000528:radiation effects*; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism; D005720:Gamma Rays; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D017930:Genes, Reporter; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction / Q000528:radiation effects; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D037483:Galectin 1; C468783:H2AX protein, human; D006657:Histones; D034741:RNA, Small Interfering; D004247:DNA; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins