Abstract:
:Activating beta-catenin mutations with aberrant cytoplasmic and nuclear protein accumulation are hallmarks of adamantinomatous craniopharyngiomas (adaCP). These tumours tend to be associated with unfavourable and occasionally disastrous sequelae, as they invade adjacent brain structures such as the hypothalamus. The peculiar digitate growth pattern does not always allow gross surgical removal often leading to recurrence. The tips of invading adaCP epithelium harbour cell clusters with nuclear beta-catenin accumulations, suggesting an influence of beta-catenin-dependent signal transduction on the tumour migratory capacity. This hypothesis was tested by suppressing beta-catenin expression in six primary human adaCP cell cultures using small interfering RNA (siRNA) directed against the beta-catenin gene (CTNNB1). Tumour cell migration was significantly reduced in Boyden chamber and wound-healing experiments following siRNA treatment. We further showed that fascin, a target gene of beta-catenin TCF signalling in colorectal cancer cells and a key component of filopodia, is also involved in this process. beta-Catenin accumulating tumour cells co-express fascin and fascin mRNA levels can be significantly down-regulated in adaCP cultures treated with CTNNB1 siRNA. Furthermore, migration experiments showed a significantly lower cell motility of adaCP tumour cells in vitro when transfected with fascin siRNA. This suggests that activated Wnt-signalling serves as a promoter of the epithelial migration machinery by regulating target molecules such as fascin in adaCP tumour cells.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Hölsken A,Buchfelder M,Fahlbusch R,Blümcke I,Buslei Rdoi
10.1007/s00401-010-0642-9subject
Has Abstractpub_date
2010-05-01 00:00:00pages
631-9issue
5eissn
0001-6322issn
1432-0533journal_volume
119pub_type
杂志文章abstract::The presence and distribution of human immunodeficiency virus (HIV) were examined in the CNS of two children with severe HIV encephalitis and myelitis. Using polymerase chain reaction-mediated DNA amplification and subsequent Southern analysis, proviral HIV gag sequences were identified in brain tissue of both patient...
journal_title:Acta neuropathologica
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