Transduction of wild-type merlin into human schwannoma cells decreases schwannoma cell growth and induces apoptosis.
Mutations in both alleles of the tumour suppressor gene coding for merlin/schwannomin, an ERM family protein, cause the hereditary disease neurofibromatosis type 2 (NF2). NF2 is characterized by the development of multiple nervous system tumours especially vestibular schwannomas. Efficient oncoretrovirus-mediated gene transfer of different merlin constructs was used to stably re-express wild-type merlin in primary cells derived from human schwannomas. Using two-parameter FACS analysis we show that expression of wild-type merlin in NF2 cells led to significant reduction of proliferation and G0/G1 arrest in transduced schwannoma cells. In addition, we show increased apoptosis of schwannoma cells transduced with wild-type merlin. Our findings in primary schwannoma cells from NF2 patients strongly support the hypothesis of merlin acting as a tumour suppressor and may help in understanding development of human schwannomas in NF2.
Schulze
K M M
KM
Molecular Neurobiology Laboratory, Department of Neurology, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
Hanemann
C O
CO
Müller
H W
HW
Hanenberg
H
H
D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009442:Neurilemmoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D025581:Neurofibromin 2 / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic
D008164:Luminescent Proteins; D009363:Neoplasm Proteins; D025581:Neurofibromin 2; D049452:Green Fluorescent Proteins