Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma

Sunpaweravong, Patrapim; Sunpaweravong, Somkiat; Puttawibul, Puttisak; Mitarnun, Winyou; Zeng, Chan; Barón, Anna E.; Franklin, Wilbur A.; Said, Sherif; Varella‐Garcia, Marileila

doi:10.1007/s00432-004-0610-7

Cited by 127 publications

(80 citation statements)

References 24 publications

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“…We totally agree with them about the fact that several analyses of HER2 carried out by immunohistochemistry or other methods (Shiga et al, 1993;Hardwick et al, 1997;Tanaka et al, 1997;Friess et al, 1999;Wang et al, 1999;Akatmatsu et al, 2003;Miyazono et al, 2004;Mimura et al, 2005a, b;Sato et al, 2005;Sunpaweravong et al, 2005) have all found rates of overexpression greater than 2.8%. To our opinion, the differences observed between these different studies have several origins: the first of them, as clearly said by Khan and coworkers is the high heterogeneity in the methodologies used in the collection of studies cited by these authors.…”

supporting

confidence: 83%

Reply: Her2 (ErbB2) receptors, a potential therapeutic target in squamous cell carcinoma of oesophagus?

et al. 2006

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supporting

confidence: 83%

Reply: Her2 (ErbB2) receptors, a potential therapeutic target in squamous cell carcinoma of oesophagus?

et al. 2006

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“…This result was the high-end of the data in literature showing HER-2 expression in oesophageal SCC varying between 0 and 31% (Sunpaweravong et al, 2005), in which the different rate of HER-2 expression seems to be due to the different criteria for evaluating the results. Importantly, both EGFR-and HER-2-positive tumours were observed in 18% of all patients, out of which 75% showed EGFR and HER-2 expression in individually distinct regions.…”

Section: Discussionmentioning

confidence: 49%

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

et al. 2007

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We previously reported that oesophageal squamous cell carcinoma (SCC) had a relatively high incidence of EGFR and HER-2 overexpression. Thus, anti-HER family targeting may become a promising approach to treat oesophageal SCC. In the present study, we investigated (a) the distribution of EGFR and HER-2 expression in oesophageal SCC (n ¼ 66) detected by immunohistochemistry and (b) cetuximab-and/or trastuzumab-mediated biological activity (antiproliferative effect by the MTT assay, apoptosis-inducing activity by the annexin V/propidium iodide assay, and antibody-dependent cellular cytotoxicity (ADCC) by the 51 Cr-release assay) against oesophageal SCC cell lines with various levels of EGFR and HER-2. Twelve of the 66 patients (18%) showed both EGFR-and HER-2 expression. Out of both EGFR-and HER-2-positive cases, nine cases (75%) showed EGFR and HER-2 expression in individually distinct regions. Furthermore, the combination of cetuximab and trastuzumab could induce synergistic antiproliferative effects and additional ADCC activities against not all, but several oesophageal SCC cell lines with EGFR and HER-2 expression. The combination of cetuximab and trastuzumab may be useful in the treatment of oesophageal SCC with EGFR and HER-2 expression.

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“…INK4a (40%-50%) tumor suppressor genes, and human telomerase (hTERT) activation (Mandard et al 2000;Metzger et al 2004;Sunpaweravong et al 2005). Cyclin D1 and EGFR overexpression appears to be associated with early events in tumor initiation, in particular with preneoplastic (squamous dysplasia) and early neoplastic stages, whereas p53 and p16 inactivation is associated with tumor progression in advanced neoplastic stages (Mandard et al 2000;Okano et al 2003).…”

mentioning

confidence: 99%

The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation

Okawa¹,

Michaylira²,

Kalabis³

et al. 2007

Genes Dev.

160

161

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Esophageal cancer is a prototypic squamous cell cancer that carries a poor prognosis, primarily due to presentation at advanced stages. We used human esophageal epithelial cells as a platform to recapitulate esophageal squamous cell cancer, thereby providing insights into the molecular pathogenesis of squamous cell cancers in general. This was achieved through the retroviral-mediated transduction into normal, primary human esophageal epithelial cells of epidermal growth factor receptor (EGFR), the catalytic subunit of human telomerase (hTERT), and p53 R175H, genes that are frequently altered in human esophageal squamous cell cancer. These cells demonstrated increased migration and invasion when compared with control cells. When these genetically altered cells were placed within the in vivo-like context of an organotypic three-dimensional (3D) culture system, the cells formed a high-grade dysplastic epithelium with malignant cells invading into the stromal extracellular matrix (ECM). The invasive phenotype was in part modulated by the activation of matrix metalloproteinase-9 (MMP-9). Using pharmacological and genetic approaches to decrease MMP-9, invasion into the underlying ECM could be suppressed partially. In addition, tumor differentiation was influenced by the type of fibroblasts within the stromal ECM. To that end, fetal esophageal fibroblasts fostered a microenvironment conducive to poorly differentiated invading tumor cells, whereas fetal skin fibroblasts supported a well-differentiated tumor as illustrated by keratin "pearl" formation, a hallmark feature of well-differentiated squamous cell cancers. When inducible AKT was introduced into fetal skin esophageal fibroblasts, a more invasive, less-differentiated esophageal cancer phenotype was achieved. Invasion into the stromal ECM was attenuated by genetic knockdown of AKT1 as well as AKT2. Taken together, alterations in key oncogenes and tumor suppressor genes in esophageal epithelial cells, the composition and activation of fibroblasts, and the components of the ECM conspire to regulate the physical and biological properties of the stroma.[Keywords: Cell migration and invasion; tumor microenvironment; EGFR; p53; MMP-9; AKT] Supplemental material is available at http://www.genesdev.org. Received February 22, 2007; revised version accepted September 5, 2007. 8 These authors contributed equally to this work. 9Corresponding author. E-MAIL anil2@mail.med.upenn.edu; FAX (215) 573-5412. Article is online at http://www.genesdev.org/cgi

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Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma

Cited by 127 publications

References 24 publications

Reply: Her2 (ErbB2) receptors, a potential therapeutic target in squamous cell carcinoma of oesophagus?

Reply: Her2 (ErbB2) receptors, a potential therapeutic target in squamous cell carcinoma of oesophagus?

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation

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