Transduction of wild-type merlin into human schwannoma cells decreases schwannoma cell growth and induces apoptosis.

Abstract

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.

• Authors: K M M Schulze, C O Hanemann, H W Müller, H Hanenberg
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 11 Issue 1 Pg. 69-76 (Jan 01 2002) ISSN: 0964-6906 [Print] England
• PMID: 11773000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Luminescent Proteins
• Neoplasm Proteins
• Neurofibromin 2
• Green Fluorescent Proteins

Topics

• Apoptosis
• Blotting, Western
• Cell Cycle (physiology)
• Cell Division
• Cells, Cultured
• Flow Cytometry
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Genetic Vectors
• Green Fluorescent Proteins
• Humans
• Luminescent Proteins (metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Neurilemmoma (genetics, metabolism, pathology)
• Neurofibromin 2 (genetics, metabolism)
• Retroviridae (genetics)
• Transduction, Genetic