Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma

Pavey, Sandra, Zuidervaart, Wieke, van Nieuwpoort, Frans, Packer, Leisl, Jager, Martine, Gruis, Nelleke and Hayward, Nicholas (2006) Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma. Melanoma Research, 16 4: 285-296. doi:10.1097/01.cmr.0000222589.30117.f2


Author Pavey, Sandra
Zuidervaart, Wieke
van Nieuwpoort, Frans
Packer, Leisl
Jager, Martine
Gruis, Nelleke
Hayward, Nicholas
Title Increased p21-activated kinase-1 expression is associated with invasive potential in uveal melanoma
Journal name Melanoma Research   Check publisher's open access policy
ISSN 0960-8931
1473-5636
Publication date 2006-08
Sub-type Article (original research)
DOI 10.1097/01.cmr.0000222589.30117.f2
Volume 16
Issue 4
Start page 285
End page 296
Total pages 12
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams and Wilkins
Language eng
Subject 111201 Cancer Cell Biology
111301 Ophthalmology
111203 Cancer Genetics
Abstract Prognosis in patients with uveal melanoma is poor as approximately half of all tumors metastasize and currently there are no effective treatments for disseminated disease. Differences in invasiveness between uveal melanomas could therefore be of major significance regarding clinical outcome. To identify genes associated with invasive potential, we have used microarray expression profiling combined with phenotypic characterization of uveal melanoma and melanocyte cell lines to define a gene signature associated with cellular invasion. A panel of 14 uveal cell cultures was assessed using three assays of invasiveness: matrigel invasion chamber system, scratch wound closure and cell motility. We identified a set of 853 differentially expressed transcripts (Wilcoxon–Mann–Whitney test, P<0.01) that discriminated between samples with high or low invasive capacity based on a composite phenotype that takes into account behavior across all three assays. Of particular interest, expression of two members of the p21-activated kinase (PAK) family, PAK1 and PAK7, was elevated in the more invasive cultures. PAK1 has previously been shown to play a central role in regulating cell motility and invasiveness in other cell types, and increased expression has been observed in breast and colorectal carcinomas. Using small interfering RNA-mediated PAK1 knockdown, we showed up to a five-fold decrease in invasion through matrigel, indicating that elevated levels of PAK1 are associated with invasive potential in uveal melanoma. These data implicate PAK1 as a potential new target for therapy of these tumors.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Thu, 12 Feb 2009, 15:51:27 EST by Alexandra Cooney on behalf of Medicine - Royal Brisbane and Women's Hospital