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Selective upregulation and amplification of the lysyl oxidase like‐4 (LOXL4) gene in head and neck squamous cell carcinoma
Author(s) -
Görögh T,
Weise JB,
Holtmeier C,
Rudolph P,
Hedderich J,
Gottschlich S,
Hoffmann M,
Ambrosch P,
Csiszar K
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2137
Subject(s) - lysyl oxidase , head and neck squamous cell carcinoma , biology , extracellular matrix , cancer research , pathology , microbiology and biotechnology , cancer , head and neck cancer , medicine , genetics
Members of the lysyl oxidase family (LOX) are copper and lysyl‐tyrosine quinone cofactor‐containing amine oxidases that are important for the assembly and maintenance of components of the extracellular matrix. Our previous results demonstrated that a novel member, LOXL4 , is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. Results of the current study showed overexpression of the LOXL4 transcript in 74% (46 of 62) of invasive HNSCC tumours and 90% of both primary and metastatic HNSCC cell lines. Significant correlation was found between LOXL4 expression and local lymph node metastases versus primary tumour types ( p < 0.01) and higher tumour stages ( p < 0.01). Immunocytochemistry demonstrated cellular overexpression of the LOXL4 protein that correlated with the increased mRNA transcription in HNSCC cells. HNSCC cell lines displayed in significant subset of nuclei increased copies of the LOX4 gene locus on chromosome 10q24, demonstrated by fluorescence in situ hybridization (FISH). Extensive metaphase cytogenetic analysis was performed on UTSCC19A cells, identifying an isochromosome i(10)(q10). Taken together, these results highlight LOXL4 expression as a distinctive trait and suggest a functional role for LOXL4 in the molecular pathogenesis of invasive head and neck carcinomas. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.