Global gene expression profiles of human head and neck squamous carcinoma cell lines

Abstract

For genomewide monitoring and identification of biomarkers of head and neck squamous cell carcinoma (HNSCC), we have conducted a systematic characterization of gene expression profiles, using human cDNA microarrays containing 9K clones, in 25 HNSCC cell lines and 1 immortalized human oral keratinocyte cell line. We used normal human oral keratinocytes (NHOKs) as a reference. Our study showed that genes primarily involved in cell cycle regulation, oncogenesis, cell proliferation, differentiation, apoptosis and cell adhesion were widely altered in the 26 cell lines. Upregulated genes included known oncogenes, protein kinases, DNA-binding proteins and cell cycle regulators, while those commonly downregulated included differentiation markers, cell adhesion proteins, extracellular matrix proteins, structural proteins (keratins) and protease inhibitor proteins. Compared to NHOK, we observed a striking reduction in the expression of genes involved in terminal differentiation, suggesting that a loss in this process is an important signature of HNSCC. Key words: microarrays; head and neck squamous cell carcinoma; gene expression; tumor progression; oral cancer; biomarkers; differentiationHead and neck cancers represent the 6th most common human neoplasm in the developed world, resulting in 13,000 deaths each year in the United States alone, and amount to 5% of all newly diagnosed cancer cases in Northern and Western European countries. 1-3 More than 90% of this cancer type are of squamous origin and common sites include hypopharynx, larynx, oral cavity, nasopharynx, oropharynx, paranasal sinus, nasal cavity, parathyroid and salivary glands. 4 Despite recent advances in treatment, the long-term survival rate of head and neck squamous cell carcinoma (HNSCC) patients has remained at 50% with high rates of associated mortality. 5 Late presentation of lesions, lack of suitable markers for early detection and failure of advanced lesions to respond to available chemotherapy contribute to a poor outcome of HNSCC. The poor prognosis of HNSCC patients may also be a reflection of the fact that, while the major risk factors involved in HNSCC pathogenesis, such as alcohol and tobacco, are well recognized, 6 little is known on the molecular mechanisms underlying this type of cancer.The development of HNSCC is a multistep process accompanied by genetic and epigenetic changes, including loss of heterozygosity, gene inactivation by methylation and gene amplification, all of which can alter gene expression. 7 For instance, the most frequent cytogenetic alterations in HNSCC are gains of 3q, 8q, 20q, 7p, 11q13 and 5p and losses in 3p, 9p, 21q, 5q, 13q, 18q and 8p. 8 In these loci, there are genes that encode specific functional classes of proteins such as cell cycle regulators, tumor suppressors, cell adhesion molecules including integrin, and protein kinases. 9 -11 Furthermore, a role for Epstein-Barr virus (EBV) and human papillomavirus (HPV) 16 and 18 in certain HNSCC lesions has been reported. 12 For instance, EBV is now known to play ...

Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation

“…The Eps8 upregulation promotes cell migration and invasion LF Yap et al OSCC cell lines could be distinguished from normal cells based on the expression pattern of this set of genes. Consistent with previous microarray studies of OSCC, this study showed the deregulated expression of various keratin genes, together with cell adhesion molecules and differentiation markers, supporting the general notion that loss of cell structure and differentiation is a critical step in the development of oral cancer (Al Moustafa et al, 2002;Jeon et al, 2004). Furthermore, the expression of a number of specific genes showed similar changes to those reported in previous studies, namely syndecan-1, stratifin, FAT2, interleukin-1 receptor antagonist, secreted frizzled related protein 1 and aldehyde dehydrogenase (Alevizos et al, 2001;Al Moustafa et al, 2002;Cromer et al, 2004;Jeon et al, 2004).…”

Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas

“…[27][28][29][30] In the case of breast cancer studies, a set of 70 genes correctly predicted the nature and progression of the disease as well as the outcome. 29,30 These studies support the idea that changes in the molecular profiles of gene expression are early events during carcinogenesis and such global expression profiles can be used effectively to predict the course of the disease.…”

UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes

“…Such a mechanism has recently been demonstrated for arabidopsis [8]. The expression of huCOP1 is altered in non-melanoma skin cancers [34] and several members of the identified regulatory network have been implicated in the pathogenesis of these skin diseases [35][36][37][38]. Thus, huCOP1 emerges as a potential target molecule for BCC and/or SCC.…”

“…Moreover, well established data are available on the differential expression of several members of the identified huCOP1-mediated UVB-responsive network both in BCC and SCC ( [34][35][36][37][38] ).…”