Identification of 9 Genes Differentially Expressed in Head and Neck Squamous Cell Carcinoma

González, Hernán; Gujrati, Manu; Frederick, Mitchell J.; Henderson, Ying C.; Jayakumar, Arumugam; SPRING, P; Mitsudo, Kenji; Kim, Hyung Woo; Clayman, Gary L.

doi:10.1001/archotol.129.7.754

Cited by 94 publications

(81 citation statements)

References 29 publications

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“…In fact, as determined by the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, an average of 4.6-, 6.4-and 22.1-fold decrease in ZNF185 transcript level was observed in intermediate grade (Gleason score 6), high-grade (Gleason score 9) and metastatic tumors, respectively, when compared with benign epithelia (Vanaja et al, 2003). In support of our observation in PCa, recent studies from other groups suggest that severely decreased levels of ZNF185 transcript are common in lung primary tumors as well as in head and neck squamous cell carcinoma (Gonzalez et al, 2003;Medina et al, 2005). In lung tumors, the ZNF185 gene was identified as a transcriptional target of the Brg-1-containing human switch/ sucrose non-fermenting complex (Medina et al, 2005).…”

Section: Introductionsupporting

confidence: 89%

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ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

2006

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We have recently identified ZNF185 as a gene that is downregulated in prostate cancer (PCa), in part via epigenetic alteration, and maybe associated with disease progression. In this study, we cloned the ZNF185 cDNA from normal human prostate tissues and investigated its biological function. We show that ZNF185 is a novel actin-cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain-containing protein that localizes to F-actin structures, and is enriched at focal adhesions. We find that the NH 2 -terminal region, which we designate the actintargeting domain, facilitates ZNF185 binding to actin in vitro and is both necessary and sufficient to mediate actin-cytoskeleton targeting of ZNF185, whereas the LIM domain, which is localized in the COOH-terminus is dispensable for this phenomenon. Interestingly, ectopic expression of full-length ZNF185, but not a mutant lacking the actin-targeting domain, could suppress proliferation and anchorage-independent growth of PCa cells. Together, our data suggest that ZNF185 may function as a tumor-suppressor protein by associating with the actincytoskeleton.

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Section: Introductionsupporting

confidence: 89%

“…The frequent transcriptional inactivation in various tumors also implicates a role of ZNF185 gene in tumorigenesis (Gonzalez et al, 2003;Vanaja et al, 2003;Medina et al, 2005;Wong et al, 2005). Actin re-organization participates in aspects of cell proliferation including gene transcription and cytokinesis.…”

Section: Discussionmentioning

confidence: 99%

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

2006

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“…Periostin is originally identified from osteoblasts and functions as a cell adhesion molecule for preosteoblast and to participate in osteoblast recruitment, attachment and spreading (Takeshita et al, 1993;Horiuchi et al, 1999). Previous studies showed that the expression of Periostin is upregulated in various types of cancer, including head and neck (Gonzalez et al, 2003), colon , Tai et al, 2005, breast , lung (Sasaki et al, 2001c) and ovarian cancer (Gillan et al, 2002). Here, we also found that 68% of OSCC cases expressed Periostin mRNA and 69% of OSCC cases expressed Periostin protein.…”

Section: Discussionmentioning

confidence: 99%

Periostin is frequently overexpressed and enhances invasion and angiogenesis in oral cancer

et al. 2006

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Oral squamous-cell carcinoma (OSCC) is one of the most common types of human cancer. Typically OSCC cells show persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. We previously identified Periostin as the gene demonstrating the highest fold change expression in the invasive clone by comparing the transcriptional profile of parent OSCC cell line and a highly invasive clone. Here, we demonstrated that Periostin overexpression enhanced invasiveness in oral cancer cell lines. To know the role of Periostin in invasion, angiogenesis and metastasis in OSCC cases, we first examined the expression of Periostin mRNA in 31 OSCC cases by RT -PCR and Periostin protein in 74 OSCC cases by immunohistochemistry. Then, we compared the Periostin expression with invasion pattern, metastasis and blood vessel density. Periostin mRNA and protein overexpression were frequently found in OSCC cases and Periostin expression was well correlated with the invasion pattern and metastasis. Moreover, blood vessel density of Periostin-positive cases was higher than those of Periostin-negative cases. Interestingly, recombinant Periostin enhanced capillary formation in vitro in a concentration-dependant manner. In summary, these findings suggest that Periostin may promote invasion and angiogenesis in OSCC, and that Periostin can be a strong marker for prediction of metastasis in oral cancer patients.

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“…We generated the signature gene set using a widely accepted statistical method, SAM, that selects genes that are differentially expressed between two groups and estimates a false discovery rate (Tusher et al, 2001). Due to the wide variation in published gene signatures even pertaining to the relatively narrow question of transformation in HNSCC, we considered the accurate prediction of an independent validation set essential to evaluating our results (Alevizos et al, 2001;Mendez et al, 2002;Gonzalez et al, 2003;Hwang et al, 2003;Leethanakul et al, 2003;Ntzani and Ioannidis, 2003). Principal-components analysis is also a useful visual tool but is not considered a robust predictor, and in our hands showed a trend differentiating NÀ from N þ .…”

Section: Discussionmentioning

confidence: 99%

“…HNSCC may be a useful system for studying lymphatic metastasis because of the high probability of lymphatic spread and low probability of hematogenous spread. A recent study has identified a gene signature for recurrent disease in HNSCC and several studies have investigated the changes in gene expression from normal tissue to carcinoma, but studies involving lymphatic metastasis have been limited by the small number of genes assessed and/or lack of a rigorous efficacy test of the metastatic signature (Alevizos et al, 2001;Belbin et al, 2002;Mendez et al, 2002;Hwang et al, 2003;Gonzalez et al, 2003;Leethanakul et al, 2003;Nagata et al, 2003;Chung et al, 2004;Ginos et al, 2004;Schmalbach et al, 2004;Warner et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

et al. 2004

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Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.

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Identification of 9 Genes Differentially Expressed in Head and Neck Squamous Cell Carcinoma

Abstract: Using differential display and microarray analysis, we have identified and confirmed the differential expression of 9 genes in HNSCC. Work is in progress to determine the biological significance of these genes and their potential as biomarkers or targets for therapy.

Cited by 94 publications

References 29 publications

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

ZNF185, an actin–cytoskeleton-associated growth inhibitory LIM protein in prostate cancer

Periostin is frequently overexpressed and enhances invasion and angiogenesis in oral cancer

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

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