Role of the aspartyl-asparaginyl-β-hydroxylase gene in neuroblastoma cell motility

被引:56
作者
Sepe, PS
Lahousse, SA
Gemelli, B
Chang, H
Maeda, T
Wands, JR
de la Monte, SM
机构
[1] Brown Univ, Rhode Isl Hosp, Sch Med, Liver Res Ctr,Dept Med, Providence, RI 02903 USA
[2] Brown Univ, Rhode Isl Hosp, Sch Med, Dept Pathol, Providence, RI 02903 USA
关键词
D O I
10.1097/01.LAB.0000020406.91689.7F
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aspartyl (asparaginyl) beta-hydroxylase (AAH) is overexpressed in various malignant neoplasms, and high levels of immunoreactivity mainly occur in infiltrating or metastasized tumors. In addition, AAH is abundantly expressed in normally invasive placental trophoblastic cells. These observations led to the hypothesis that AAH may have a role in motility and aggressive behavior of tumor cells. The present study demonstrates that AAH is overexpressed in primary human malignant neuroectodermal tumors, including medulloblastomas and neuroblastomas, and that AAH expression is at a low level or undetectable in the normal mature brain. In the Sy5y neuroblastoma cell line, endogenous expression of the similar to86-kd AAH protein was demonstrated by Western blot analysis, and immunoreactivity predominantly localized to the cell surface by immunocytochemical staining and FAGS analysis. Sy5y cells that were stably transfected with the human AAH cDNA had increased levels of proliferating cell nuclear antigen and Bcl-2, and reduced levels of p21/Waf1 and p16. In addition, increased AAH expression enhanced Sy5y cell motility, whereas antisense oligodeoxynucleotide inhibition of AAH significantly reduced Sy5y cell motility and increased the levels of p21/Waf1 and p16. The findings suggest that AAH overexpression contributes to the malignant phenotype of neuroectodermal tumor cells by increasing motility and enhancing proliferation, survival, and cell cycle progression. Because AAH expression is at a low level or undetectable in normal brain, the AAH gene may be a target for treating primitive neuroectodermal tumors.
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页码:881 / 891
页数:11
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