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Amplification and overexpression of PPFIA1 , a putative 11q13 invasion suppressor gene, in head and neck squamous cell carcinoma
Author(s) -
Tan Kaia Davis,
Zhu Yansong,
Tan Hiang Khoon,
Rajasegaran Vikneswari,
Aggarwal Amit,
Wu Jeanie,
Wu Hui Yong,
Hwang Jacqueline,
Lim Dennis T. H.,
Soo Khee Chee,
Tan Patrick
Publication year - 2008
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20539
Subject(s) - head and neck squamous cell carcinoma , amplicon , biology , carcinogenesis , gene knockdown , cancer research , cell culture , tumor suppressor gene , downregulation and upregulation , gene , cancer , microbiology and biotechnology , head and neck cancer , genetics , polymerase chain reaction
Chromosomal amplifications of the 11q13 genomic region are frequent in head and neck squamous cell carcinoma (HNSCC). To identify novel 11q13 amplification targets, we integrated high-resolution array-based comparative genomic hybridization and Affymetrix gene-expression profiling of eight HNSCC cell lines. We found that PPFIA1 was the highest upregulated gene in the 11q13 amplicon of HNSCC cell lines when compared with HNSCC lines without 11q13 amplification and confirmed the upregulation of PPFIA1 in primary HNSCCs by real-time PCR. Using siRNA knockdown, we investigated PPFIA1 function in three HNSCC lines using both in vitro invasion assays and wound-healing assays. Surprisingly, we found that cancer cells become more invasive when the PPFIA1 protein levels were reduced, suggesting that PPFIA1 may act as an invasion inhibitor in HNSCC. This unexpected result suggests that the 11q13 amplicon may comprise both positive and negative regulators involved in HNSCC. Our study is the first to evaluate the role of PPFIA1 in head and neck carcinogenesis and suggests a potential link between PPFIA1 activity and cell-extracellular matrix interactions. This article contains supplementary material available via the Internet at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.