Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression profiling

Shimizu, Shun; Seki, Naohiko; Sugimoto, Takashi; Horiguchi, Susumu; Tanzawa, Hideki; Hanazawa, Toyoyuki; Okamoto, Yoshitaka

doi:10.3892/or.18.6.1489

Cited by 31 publications

(38 citation statements)

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“…Putative target genes in HNSCC were identified after direct integration of chromosome alteration and gene expression data, using bioinformatics analysis to specifically identify those gene expression change events associated with copy number alterations (Jarvinen et al, 2006). Our previous work also suggested that the identification of affected genes in chromosomal alteration loci are important to further the understanding of tumorgenesis and progression in SCC (Shimizu et al, 2007;Sugimoto et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma

Sugimoto

Seki

Shimizu

et al. 2008

Genes Chromosomes & Cancer

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To identify putative biomarkers in squamous cell carcinoma (SCC), a survey of parallel chromosomal alterations and gene expression studies in 10 SCC cell lines were performed using array-comparative genomic hybridization (CGH) and oligo-microarray techniques. The most frequent changes were gains of 11q13.1-13.3 and losses of 18q12.1-23 in SCC. Furthermore, the expression levels of the sets of genes at both these loci in SCC were measured using microarray analysis. By combining the array-CGH with the microarray data, 10 genes at 11q13.1-13.3 and 6 genes at 18q12.1-23 whose expression correlated with chromosomal alterations were identified. To verify the expression levels of the identified genes, we used expression analysis data derived from our earlier study of clinical specimens. In clinical samples, six genes (GAL, GSTP1, MRPL11, MRPL21, SF3B2, and YIF1A) at 11q13.1-13.3 and one gene (GALR1) at 18q23 showed a significant difference between normal and tumor samples. GAL, coding for the neuropeptide galanin, and GALR1, a galanin receptor, were identified as candidate genes of oncogenesis in SCC. The expression levels of GAL, GALR1, GALR2, and GALR3 were confirmed by real-time PCR. The expression ratio between GAL and GALR1 showed a significant negative correlation. GALR1 is a G-protein-coupled receptor that activates GTP-binding proteins to trigger signaling cascades such as the mitogen-activated protein kinase pathway, and is a well-established mitogenic pathway. This further supports the hypothesis that the genes involved in the GAL signaling cascade are candidates for regulation of oncogenesis in SCC.

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Section: Introductionmentioning

confidence: 99%

The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma

Sugimoto

Seki

Shimizu

et al. 2008

Genes Chromosomes & Cancer

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“…Czerninski et al's findings further support targeting the mTOR pathway as a chemoprevention strategy. Other potential targets for chemoprevention besides mTOR (18) include AKT (14,19,20), cyclooxygenase-2, and EGFR (21,22). The overexpression and activation of these molecules in precancerous lesions and tumors in this mouse model suggests its usefulness for evaluating new drugs that modulate these targets.…”

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confidence: 99%

“…Numerous studies have focused on identifying the genetic and epigenetic alterations underlying HNSCC (13)(14)(15)(16). Further mutational and genomic analysis of precancerous lesions and tumors induced in the oral-specific mouse model could unveil which lesions are most susceptible to specific chemopreventive agents; for example, whether oral lesions with p53 mutations or cyclin-dependent kinase 2A mutations have enhanced susceptibility to rapamycin.…”

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confidence: 99%

Oral-Specific Chemical Carcinogenesis in Mice: An Exciting Model for Cancer Prevention and Therapy

Wong

2009

Cancer Prevention Research

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Editor's Note: Preclinical animal models that are clinically relevant to and suitable for cancer chemoprevention research are beginning to emerge. Because of the critical importance of these models, we are publishing this second perspective on the modeling article by Czerninski et al. in this issue of the journal. Whereas the perspective by Dennis focuses on translating mammalian target of rapamycin targeting in animal models into clinical preventive drug development, this "different" perspective focuses on strengths of the new mouse model of Czerninski et al.-oral specificity and chemical induction and diversity of heterogeneity of lesions-as a clinically relevant animal model that overcomes certain limitations of other animal models for oral cancer chemoprevention.Humans are constantly bombarded with physical, chemical, and biological insults-such as UV radiation, toxic chemicals, and pathogens-that can damage DNA, activate oncogenic pathways, and cause inflammation. These damages can lead to precancerous lesions that can become malignant. Whether such precancerous lesions can be prevented and whether the progression of precancerous lesions to malignant neoplasms can be controlled have been the subjects of intense research. Despite great interest in cancer chemoprevention, however, relatively few animal models have been developed or are available for testing chemopreventive strategies. In this issue of the journal, Czerninski et al. (1) describe an oral-specific chemical carcinogenesis mouse model that shows the development of precancerous lesions into malignant squamous cell carcinomas (SCC). The relevance of this oral-specific model to cancer prevention research is substantiated by its pathologic features and molecular alterations including the activation of epidermal growth factor receptor (EGFR), cyclooxygenase-2, and the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in tumors, which recapitulate what has been found in clinical samples. The model could provide a new platform for validating molecular-targeted chemopreventive strategies (1).Czerninski et al.(1) treated mice with 4-nitroquinoline-1 oxide (4NQO), a DNA adduct-forming agent causing DNA damage mimicking that induced by cigarette smoke, for 16 weeks. At the end of 4NQO treatment, 100% of the mice exhibited precancerous lesions and/or tumors in their tongues and oral mucosa. Many of these lesions progressed to malignant SCC even after 4NQO was withdrawn. When the mice were treated with rapamycin, however, the progression of oral precancerous lesions to malignant SCC was greatly reduced; more striking, some SCCs regressed. Therefore, Czerninski et al.'s study supports further developing drugs that target the mTOR pathway to prevent precancerous lesions from progressing to malignant SCC in the oral cavity, and potentially, other tumor types with deregulated mTOR pathway. Testing whether precancerous lesions can be prevented if mice are treated at an earlier stage is one attractive possibility; for instance, mice could be treate...

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“…INHBA is a subunit of the complex that inhibits pituitary FSH secretion. Overexpression of INHBA is reported in various cancers including gastric cancer [20,24,25], glioblastoma [26], lung adenocarcinoma [27], esophageal adenocarcinoma [28], tongue squamous cell carcinoma [20], head and neck squamous cell carcinoma [29] and pancreatic adenocarcinoma [30]. Overexpression of INHBA is associated with poor survival in gastric cancer [27], lung adenocarcinoma [27] and head and neck squamous cell carcinomas [29].…”

Section: Inhibin Beta a Is Overexpressed In A Subset Ofmentioning

confidence: 99%

Evaluation of protein expression pattern of stanniocalcin 2, insulin-like growth factor-binding protein 7, inhibin beta A and four and a half LIM domains 1 in esophageal squamous cell carcinoma

Kashyap

Pawar

Keerthikumar

et al. 2013

CBM

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Abstract. The pathogenesis of esophageal squamous cell carcinoma (ESCC) involves both genetic and environmental factors. Previously, we have carried out gene and protein expression profiling of ESCC using DNA microarrays and mass spectrometrybased quantitative proteomics, respectively. These studies resulted in identification of several potential biomarkers of ESCC, some with known reports of differential expression in the scientific literature and others that were novel observations from our studies. We report systematic validation of selected markers from our studies on a larger cohort of cancer tissue sections by immunohistochemical labeling of tissue microarrays. We have validated expression of insulin-like growth factor-binding protein 7 (IGFBP7), stanniocalcin 2 (STC2), inhibin beta A (INHBA) and four and a half LIM domains 1 (FHL1). Immunohistochemical labeling with anti-stanniocalcin 2 antibody demonstrated its overexpression in 132/140 (94%) cases, IGFBP7 showed overexpression in 127/140 (91%) cases and overexpression of INHBA was observed in 62/105 (59%) of ESCC cases. In contrast, FHL1 expression was observed only in 12/143 (8%) of ESCC cases suggesting its possible involvement in tumor suppression. These data suggest that IGFBP7, INHBA, STC2 and FHL1 might play an important role in ESCC tumorigenesis, which can be explored in future studies. Overall, our findings open up new avenues for development of novel therapeutics and/or diagnostic approaches in ESCC.

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Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression profiling

Cited by 31 publications

References 6 publications

The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma

The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma

Oral-Specific Chemical Carcinogenesis in Mice: An Exciting Model for Cancer Prevention and Therapy

Evaluation of protein expression pattern of stanniocalcin 2, insulin-like growth factor-binding protein 7, inhibin beta A and four and a half LIM domains 1 in esophageal squamous cell carcinoma

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