title: Activating transcription factor 3 is overexpressed in human glioma and its knockdown in glioblastoma cells causes growth inhibition both in vitro and in vivo.
abstract: Glioblastomas are highly malignant gliomas that are extremely invasive with high rates of recurrence and mortality. It has been reported that activating transcription factor 3 (ATF3) is expressed in elevated levels in multiple malignant tumors. The purpose of this study was to investigate the function of ATF3 in the development of glioma and its clinical significance. Immunohistochemical staining, western blot analysis and RT-qPCR revealed that the mRNA and protein levels of ATF3 and matrix metalloproteinase 2 (MMP2) were higher in the glioma than in the normal human brain tissues, and that their levels were proportional to the pathological grades. By contrast, the mRNA and protein levels of mammary serine protease inhibitor (maspin; SERPINB5) were significantly lower in the glioma than in the normal brain tissue, and maspin expression was inversely proportional to the glioma pathological grade. The transfection of U373MG glioblastoma cells with ATF3-siRNA induced a number of changes in cell behavior; the cell proliferative activity was decreased and flow cytometry revealed an increased proportion of cells arrested in the G0/G1 phase of the cell cycle. In addition, TUNEL staining indicated an increased proportion of cells undergoing apoptosis and Transwell assays revealed impaired cell mobility. The sizes of the tumors grown as xenografts in nude mice were also significantly reduced by treatment of host mice with ATF3-siRNA. Taken together, these results suggest that ATF3 promotes the progression of human gliomas.
authors: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Siqi
authors: S
authors: Ma
authors: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Changhe
authors: C
authors: Pang
authors: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Laijun
authors: L
authors: Song
authors: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Fuyou
authors: F
authors: Guo
authors: Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Hongwei
authors: H
authors: Sun
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D016193:G1 Phase; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D015843:Serpins / Q000378:metabolism
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D009363:Neoplasm Proteins; C085344:SERPIN-B5; D015843:Serpins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2