Inhibition of NF2-negative and NF2-positive primary human meningioma cell proliferation by overexpression of merlin due to vector-mediated gene transfer.
OBJECTIVE
The absence of in vitro models of neurofibromatosis Type 2 (NF2)-defective meningiomas has limited investigative efforts to study the biological effects of this gene in the pathogenesis of these tumors. The goals of this report are to show that gene transfer vectors can efficiently express the wild-type NF2 transgene into primary meningioma cells and to determine effects on cellular proliferation.


METHODS
In this study, the authors have compared the transducing capacities of a retrovirus, an adenovirus, and a herpes simplex virus amplicon vector for use in primary human meningioma cells harvested from human tumors excised from patients with and without NF2. Transduction efficiencies with the latter vector approached 100% and it was selected to transfer the wild-type NF2 transgene into these cells. Western blot analysis confirmed that vector-mediated gene transfer mediated the expression of the NF2-encoded polypeptide merlin. Overexpression of merlin significantly inhibited the proliferation of both NF2-negative and NF2-positive human meningioma cells when compared to the proliferation of cells transduced with a control vector.


CONCLUSIONS
This study demonstrates the feasibility of using vector-mediated gene transfer to study wild-type NF2 gene function in short-term cultures of primary human meningioma cells.
Ikeda
K
K
Molecular Neuro-Oncology Laboratories, Massachusetts General Hospital, Boston, USA.
Saeki
Y
Y
Gonzalez-Agosti
C
C
Ramesh
V
V
Chiocca
E A
EA
D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D016515:Genes, Neurofibromatosis 2 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008579:Meningioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D025581:Neurofibromin 2; D018139:Simplexvirus; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D025581:Neurofibromin 2