title: Enhanced radiosensitivity of NSCLC cells by transducer of erbB2.1 (TOB1) through modulation of the MAPK/ERK pathway.
abstract: Transducer of erbB2.1 (TOB1) is a member of the B-cell translocation gene (BTG)/transducer of erbB2 (TOB) anti‑proliferative protein family. Previous studies have demonstrated that overexpression of TOB1 significantly enhances the radiosensitivity of breast and cervical cancer cells. However, the potential mechanisms of TOB1 are still debated. In the present study, we evaluated the effects of infrared (IR) radiation on TOB1 expression in the human lung cancer cell lines NCI-H1975 and A549 via western blot analysis. NCI-H1975 cells were transfected with TOB1 recombinant plasmid, and A549 cells were treated with TOB1-small interfering RNA (siRNA) to establish gain-of-function and loss-of‑function cell models. The effects of radiation and TOB1 overexpression and silencing on clonogenic survival, cell cycle distribution and DNA repair were assessed. Western blot analysis was performed to determine the related mechanisms. The expression levels of TOB1 were significantly induced by IR radiation. Overexpression of TOB1 abrogated radiation-induced G2/M arrest, reduced clonogenic cell survival and enhanced γ-H2AX foci in NCI-H1975 cells exposed to irradiation. TOB1-siRNA demonstrated opposite effects in A549 cells. TOB1 regulated the activation of mitogen-activated protein kinase (MAPK) and modulated the phosphorylation of p53 via activation of the MAPK/extracellular signal-regulated kinase (ERK) pathway. The findings suggest that TOB1 may be a novel molecular target of irradiation. TOB1 modulated the radiosensitivity of lung cancer cells via the MAPK/ERK signaling pathway.
authors.affiliation: Department of Gastrointestinal Surgery Division of Thoracic Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300, PR China.
authors.forename: Ke-Kang
authors.initials: KK
authors.lastname: Sun
authors.forename: Ning
authors.initials: N
authors.lastname: Zhong
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011836:Radiation Tolerance; D015533:Transcriptional Activation / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins; D048049:Extracellular Signal-Regulated MAP Kinases