title: Expression of focal adhesion kinase in uveal melanoma and the effects of Hsp90 inhibition by 17-AAG.
abstract: BACKGROUND
  Focal adhesion kinase (FAK) is implicated in tumor progression and metastatic cascade, and has been shown to be overexpressed in a variety of human cancers. However, the role of FAK in human uveal melanoma (UM) is not well defined. The purpose of this study was to evaluate the expression of FAK in UM tumors and normal eyes, and to determine the effect of Hsp90 inhibition on FAK expression in UM cells.
  
  
  METHODS
  FAK expression was assessed in 39 UM specimens, FAK[pY397] expression was assessed in 51 UM specimens, and both FAK and FAK[pY397] expression were assessed in 20 normal eyes. The expression of FAK and FAK[pY397] was detected by Western blot in five UM cell lines after treatment with 10 μmol/L of 17-AAG.
  
  
  RESULTS
  FAK was positive in 87.2% and FAK[pY397] in 90% of UM specimens. Low FAK expression was detected in non-tumor structures and in normal eyes. The cell lines with the most proliferative, invasive phenotype (92.1, SP6.5 and MKT-BR) displayed high expression of FAK[pY397], and the levels of FAK and FAK[pY397] were decreased in the presence of 17-AAG starting with 24 h of exposure.
  
  
  CONCLUSIONS
  FAK and FAK[pY397] were overexpressed in human UM tumors compared to normal ocular tissue and high levels of FAK[pY397] were seen in the most aggressive UM cell lines. Hsp90 inhibition led to downregulation of FAK expression. We propose a role for FAK in the pathogenesis of UM. Future studies are needed to explore the use of Hsp90 inhibitors as a feasible approach for modulating FAK in UM.
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada. Electronic address: faingolddana@yahoo.com.
authors.forename: Dana
authors.initials: D
authors.lastname: Faingold
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada; Department of Ophthalmology, São Paulo Federal University - UNIFESP, São Paulo, Brazil. Electronic address: vascobravofilho@yahoo.com.br.
authors.forename: Vasco Bravo
authors.initials: VB
authors.lastname: Filho
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada. Electronic address: bruno.mtl@gmail.com.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fernandes
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada. Electronic address: ljagan@qmed.ca.
authors.forename: Lisa
authors.initials: L
authors.lastname: Jagan
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada. Electronic address: alexm_barros@yahoo.com.br.
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: de Barros
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada; Ocular Pathology Department, Anatomy Pathology Institute, University Central of Venezuela, Caracas, Venezuela. Electronic address: euorellana@gmail.com.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Orellana
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada. Electronic address: emilia.antecka@mcgill.ca.
authors.forename: Emilia
authors.initials: E
authors.lastname: Antecka
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory, Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada; Department of Ophthalmology, São Paulo Federal University - UNIFESP, São Paulo, Brazil. Electronic address: miguel.burnier@mcgill.ca.
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Burnier
mesh_terms: D016227:Benzoquinones / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Focal adhesion kinase; Hsp90; Immunohistochemistry; Uveal melanoma