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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-9-20
pubmed:abstractText
The Krüppel-like transcription factor (KLF6) gene is a tumor suppressor gene (TSG) reported to be dysregulated and inactivated through loss of heterozygosity (LOH) and/or somatic mutation in a number of major human cancers. The aim of the present study was to examine KLF6 gene status and expression in head and neck squamous cell carcinomas (HNSCC). A collection of 81 well-characterized oral and oropharyngeal HNSCC samples were analyzed for evidence of KLF6 LOH and mutation and differences in expression patterns between normal and cancerous tissues and these findings were correlated with clinicopathological variables. We also tested the effect of KLF6 inhibition in HNSCC cell lines on proliferation and p21 expression. LOH was found in approximately 30% of cases and was strongly correlated with cancer progression, tumor recurrence and decreased patient survival. Overall, median survival of patients with LOH was less than half (19 vs. 41 months, p=0.036, stratified on stage) than those without loss. Risk of death for patients with LOH was 8 times greater independent of tumor size, nodal status, tobacco smoking or treatment modality (HR 7.89, 95% CI: 1.9-32.4). Subsequent analyses revealed KLF6 mutations in only 2 of 20 samples, but altered subcellular protein localization in 64% of tumors. Targeted stable reduction of KLF6 in HNSCC cell lines increased cellular proliferation while decreasing p21 expression. Taken together, these findings suggest that KLF6 LOH represents a clinically-relevant biomarker predicting patient survival and tumor recurrence and that dysregulation of KLF6 function plays an important role in HNSCC progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2007 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1976-83
pubmed:meshHeading
pubmed-meshheading:17621627-Adult, pubmed-meshheading:17621627-Aged, pubmed-meshheading:17621627-Aged, 80 and over, pubmed-meshheading:17621627-Carcinoma, Squamous Cell, pubmed-meshheading:17621627-Cell Line, Tumor, pubmed-meshheading:17621627-Down-Regulation, pubmed-meshheading:17621627-Female, pubmed-meshheading:17621627-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17621627-Head and Neck Neoplasms, pubmed-meshheading:17621627-Humans, pubmed-meshheading:17621627-Immunohistochemistry, pubmed-meshheading:17621627-Kruppel-Like Transcription Factors, pubmed-meshheading:17621627-Loss of Heterozygosity, pubmed-meshheading:17621627-Male, pubmed-meshheading:17621627-Middle Aged, pubmed-meshheading:17621627-Proto-Oncogene Proteins, pubmed-meshheading:17621627-Recurrence, pubmed-meshheading:17621627-Survival Rate
pubmed:year
2007
pubmed:articleTitle
KLF6 allelic loss is associated with tumor recurrence and markedly decreased survival in head and neck squamous cell carcinoma.
pubmed:affiliation
Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't