Analysis of gene amplification in head‐and‐neck squamous‐cell carcinomas

Jh, Leonard; Jh, Kearsley; Chenevix-Trench, Georgia; Nk, Hayward

doi:10.1002/ijc.2910480406

Cited by 111 publications

(42 citation statements)

References 15 publications

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“…In head and neck squamous cell carcinoma, this amplification is one of the most frequently observed genetic alterations [11][12][13][14][15][16][17][18][19][20] and is reportedly correlated with aggressive tumor growth [9,13,19], the presence of lymph node metastases [17,[21][22][23], and poor prognosis [9,19,24]. The amplified 11q13 region is 3-5 megabases in size and includes four putative oncogenes: CCND1 (PRAD1), FGF3 (INT2), FGF4 (HST1), and EMS1.…”

Section: Introductionmentioning

confidence: 99%

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Yamada

Yanamoto

Rokutanda

et al. 2014

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathol

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Cortactin stimulates cell migration, invasion, and experimental metastasis. Overexpression of cortactin has been reported in several human cancers. CRK was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. We evaluated the possibility of the combination of cortactin and CRKII as an appropriate molecular target for cancer gene therapy. The expression of cortactin and CRKII in 70 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of cortactin and CRKII co-overexpression with clinicopathological factors was evaluated. Co-overexpression of cortactin and CRKII was detected in 31 of 70 oral squamous cell carcinomas, the frequency being significantly greater than in normal oral mucosa. In addition, cortactin and CRKII co-overexpression was more frequent in higher-grade cancers according to 3 the T classification, N classification, and invasive pattern. RNAi-mediated co-suppression of cortactin and CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of cortactin and CRKII expression also reduced the expression of vimentin, fibronectin, and N-cadherin. These results indicate that the co-overexpression of cortactin and CRKII may be tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that the combination of cortactin and CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. 4 1.IntroductionOral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region and accounts for more than 90% of cancers of the oral cavity [1]. The primary therapeutic modality for OSCC is surgery. Although recent advances in surgical techniques and anticancer agents have improved tumor regression and survival for patients with OSCC, wide surgical resection of OSCC inevitably causes various oral dysfunctions. Therefore, new treatment strategies are urgently needed.The presence of neck lymph node metastasis is strongly related to a poor prognosis in squamous cell carcinoma of the head and neck [2][3][4]. Moreover, it has been reported that an alteration in the expression of adhesion-related molecules is associated with poor prognosis in OSCC patients [5][6][7][8].Chromosomal band 11q13 is a frequently amplified genomic segment in a large number of malignant neoplasms, and is thought of as a potential biomarker for diagnosis and prognosis [9,10]. In head and neck squamous cell carcinoma, this amplification is one of the most frequently observed genetic alterations [11][12][13][14][15][16][17][18][19][20] and is reportedly correlated with aggressive tumor growth [9,13,19], the presence of lymph node ...

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Section: Introductionmentioning

confidence: 99%

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Yamada

Yanamoto

Rokutanda

et al. 2014

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathol

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“…genomic segment in a large number of malignant neoplasms, and is thought of as a potential biomarker for diagnosis and prognosis 12,13 .In head and neck squamous cell carcinoma, this amplification is one of the most frequently observed genetic alterations [14][15][16][17][18][19][20][21][22][23] and is reportedly correlated with aggressive tumor growth, 12,16,22 the presence of lymph node metastases, 20,[24][25][26] and poor prognosis. 12,22,27 The amplified 11q13 region is 3-5 megabases in size and includes four putative oncogenes: CCND1 (PRAD1), FGF3…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Cortactin Increases Invasion Potential in Oral Squamous Cell Carcinoma

Yamada

Yanamoto

Kawasaki

et al. 2010

Pathol. Oncol. Res.

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Cortactin stimulates cell migration, invasion, and experimental metastasis. However, the underlying mechanism is not still understood. In the present study, we therefore evaluated the possibility that cortactin could be appropriate as a molecular target for cancer gene therapy. In 70 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens, cortactin expression was evaluated by immunological analyses, and the correlations of the overexpression of cortactin with clinicopathologic factors were evaluated. Overexpression of cortactin was detected in 32 of 70 oral squamous cell carcinomas; significantly more frequently than in normal oral mucosa. Cortactin overexpression was more frequent in higher grade cancers according to T classification, N classifications, and invasive pattern. Moreover, RNAi-mediated decrease in cortactin expression reduced invasion. Downregulation of cortactin expression 4 increased the expression levels of E-cadherin, β-catenin, and EpCAM. The siRNA of cortactin also reduced PTHrP expression via EGF signaling. These results consistently indicate that the overexpression of cortactin is strongly associated with an aggressive phenotype of oral squamous cell carcinoma. In conclusion, we propose that cortactin could be a potential molecular target of gene therapy by RNAi targeting in oral squamous cell carcinoma. 5

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“…Specific genes have been associated with the development or presentation of HNSCC, but these individual alterations have failed to define prognostic or diagnostic markers (reviewed in Leonard et al (1991) and Scully et al (2000)). Addressing this issue requires large-scale analysis of gene expression profiles.…”

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confidence: 99%

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC)

Lemaire

Millon²,

Young

et al. 2003

Br J Cancer

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Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780 000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a largescale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12 -13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets.

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Analysis of gene amplification in head‐and‐neck squamous‐cell carcinomas

Cited by 111 publications

References 15 publications

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Overexpression of Cortactin Increases Invasion Potential in Oral Squamous Cell Carcinoma

Differential expression profiling of head and neck squamous cell carcinoma (HNSCC)

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