title: Role of metallothionein 1E in the migration and invasion of human glioma cell lines.
abstract: Metallothionein 1E (MT1E) has been found to be highly expressed in motile cell lines. We investigated whether MT1E actually modulates the migration and invasion of human glioma cell lines and the types of factors that have an effect on MT1E. RNA differential display was performed using Genefishing™ technology in the human glioma cell lines U343MG-A, U87MG and U87MG-10'; the results were validated by RT-PCR and northern blot analysis, in order to detect possible genetic changes as the determining factors for migration ability in malignant glioma. MT1E was identified in U87MG, a highly motile cell line. The migration and invasion abilities of human glioma cell lines, and MT1E transfectants were investigated using simple scratch testing and Matrigel invasion assays. Morphological and cytoskeletal (actin, vimentin) changes were documented by light and confocal microscopy. The expression of MT1E in four glioma cell lines was assessed by RT-PCR and western blotting. In addition, the effects of MT1E on the activity of the NF-κB p50/p65 transcription factor, MMP-2 and -9 were examined by western blotting and zymography. The endogenous MT1E expression in the human glioma cell lines was statistically correlated with their migratory abilities and invasion. The U87-MT-AS cells became more round and had decreased stress fibers, compared with the U87MG cells. Endogenous MT1E expression in the four human glioma cell lines was directly correlated with migration. Two antisense MT1E-transfected cell lines showed decreased NF-κB p50 translocation into the nucleus, which led to decreased activity of MMP-9 in conditioned media. It may be postulated that MT1E can enhance the migration and invasion of human glioma cells by inducing MMP-9 inactivation via the upregulation of NF-κB p50.
authors: Department of Brain Tumor Research Laboratory, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Republic of Korea.
authors: Hyang-Hwa
authors: HH
authors: Ryu
authors: Shin
authors: S
authors: Jung
authors: Tae-Young
authors: TY
authors: Jung
authors: Kyung-Sub
authors: KS
authors: Moon
authors: In-Young
authors: IY
authors: Kim
authors: Young-Il
authors: YI
authors: Jeong
authors: Shu-Guang
authors: SG
authors: Jin
authors: Jian
authors: J
authors: Pei
authors: Min
authors: M
authors: Wen
authors: Woo-Yeol
authors: WY
authors: Jang
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: C541541:MT1E protein, human; D052002:NF-kappa B p50 Subunit; D008668:Metallothionein; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9