Amplification of the EGF receptor and <i>c‐myc</i> genes in human esophageal cancers

Lu, Shuaiyao; Hsieh, Ling‐Ling; Luo, Feng-Chi; Weinstein, I. Bernard

doi:10.1002/ijc.2910420406

Cited by 124 publications

(58 citation statements)

References 19 publications

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“…Autocrine survival factors may also protect the tumor cells from chemotherapeutic drugs. Secretion of TGF a/EGF and overexpression of EGF receptors were not only reported in human esophageal carcinoma cell lines, but were also detected in human esophageal carcinoma tissues (Lu et al, 1988;Ozawa et al, 1987Ozawa et al, , 1989. In fact, the prognosis is poorer in esophageal cancer patients whose tumors express a higher level of EGF receptors (Iihara et al, 1993;Ozawa et al, 1989).…”

Section: Discussionmentioning

confidence: 96%

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Leu¹,

Chang²,

Hu³

2000

Oncogene

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Overexpression of epidermal growth factor receptor (EGFR) and establishment of transforming growth factor a (TGF a)/EGF autocrine system are frequently detected in tumor cells. In addition to mitogenic ability, we demonstrate in this report that EGF protects a human esophageal carcinoma (CE) cell line, CE81T/VGH, from staurosporine-induced apoptosis. The anti-apoptotic signal of EGF is alleviated by a MEK inhibitor PK98059 or an ERK2 dominant negative mutant but not by a phosphatidylinositol-3'-kinase (PI-3K) inhibitor wortmannin. Furthermore, v-raf blocks apoptosis induced by staurosporine. This evidence implies that the survival signal of EGF is mediated via the Raf-MEK-ERK pathway but not the PI3-K pathway. The survival e ect of EGF is coincident with the induction of mcl-1, an antiapoptotic gene in the bcl-2 family. PD98059 also suppresses the induction of Mcl-1 by EGF, implying that EGF may up-regulate Mcl-1 via the MAP kinase pathway. Overexpression of mcl-1 is su cient to protect against apoptosis, while transfection of a mcl-1 antisense plasmid causes cell death. The expression of mcl-1 antisense plasmid also suppresses the anti-apoptotic e ect of EGF. Taken together, these results indicate that EGF may up-regulate Mcl-1 through the MAP kinase pathway to suppress apoptosis.

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Section: Discussionmentioning

confidence: 96%

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Leu¹,

Chang²,

Hu³

2000

Oncogene

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“…[16][17][18][19] Epigenetic events, which are important in normal cellular functions, are also critical factors during initiation and progression of cancer. 20,21 Although genetic abnormalities in several oncogenes and tumor suppressor genes frequently occur in tumorigenesis, [22][23][24] our previous study showed that ECRG4 mRNA was downregulated with gene promoter hypermethylation in ESCC. 8 Tumor suppressor genes such as p14, p15, p16, FHIT, CDH1, MGMT, VHL, RASSF1A and E-cadherin are usually downregulated by gene promoter hypermethylation in ESCC.…”

Section: Discussionmentioning

confidence: 99%

Expression of esophageal cancer related gene 4 (ECRG4), a novel tumor suppressor gene, in esophageal cancer and its inhibitory effect on the tumor growth in vitro and in vivo

Yang

et al. 2009

Intl Journal of Cancer

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The ECRG4 gene was initially identified and cloned in our laboratory from human normal esophageal epithelium (GenBank accession no. AF325503). We revealed the expression of ECRG4 protein was downregulated in 68.5% (89/130) ESCC samples using tissue microarray. The low ECRG4 protein expression was significantly associated with regional lymph node metastasis, primary tumor size, and tumor stage in ESCC (p < 0.05). ECRG4 mRNA expression was downregulated in ESCC due to the hypermethylation in the gene promoter. The treatment with 5-aza-2 0 -deoxycytidine, which is a DNA methyltransferase inhibitor restored ECRG4 mRNA expression in ESCC cells. The result indicated that promoter hypermethylation may be 1 main mechanism leading to the silencing of ECRG4. The high expression of ECRG4 in patients with ESCC was associated with longer survival compared with those with low ECRG4 expression by Kaplan-Meier survival analysis (p < 0.05). ECRG4 protein was an independent prognostic factor for ESCC by multivariable Cox proportional hazards regression analysis (p < 0.05). The restoration of ECRG4 expression in ESCC cells inhibited cell proliferation, colony formation, anchorage-independent growth, cell cycle progression and tumor growth in vivo (p < 0.05). The transfection of ECRG4 gene in ESCC cells inhibited the expression of NF-jB and nuclear translocation, in addition to the expression of COX-2, a NF-jB target gene, was attenuated. Taken together, ECRG4 is a novel candidate tumor suppressor gene in ESCC, and ECRG4 protein is a candidate prognostic marker for ESCC. ' 2009 UICC

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“…Especially in ESCC, oncogenes, such as SMYD2 (1q32.3-q41), EGFR (7p12), MYC (8q24.21), CCND1 (11q13), cIAP1 (11q22) and ERBB2 (17q21.1), have already been identified as major amplification targets associated with development, progression and metastasis of aggressive disease (Lu et al, 1988;Imoto et al, 2001;Jain et al, 2007;Komatsu et al, 2009;Sato-Kuwabara et al, 2009). Among them, CCND1 is the gene most frequently amplified (22 -65%) with high copy numbers, and also associated with a poorer survival outcome in ESCC patients (Lam, 2000).…”

Section: Discussionmentioning

confidence: 99%

Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma

et al. 2010

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BACKGROUND: We aimed to develop a new biomarker to predict cyclin D1 (CCND1) status using plasma DNA in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: We evaluated the ratio of the CCND1 (11q13) dosage to the dopamine receptor D2 (DRD2; 11q22-23) dosage (C/D ratio) as CCND1 copy number. This study was divided into three steps: (1) Determination of a cutoff value for the C/D ratio in test scale; (2) Comparison of the C/D ratio in between plasma samples and cancer tissues in ESCC patients showing high plasma C/D ratio; (3) Validation study of the clinical application of the plasma C/D ratio as a diagnostic and prognostic marker, by comparing with clinicopathologic factors in 96 ESCC patients. RESULTS: The plasma C/D ratio was significantly higher in the ESCC group than the controls (P ¼ 0.0134). A high plasma C/D ratio reflected the tumour C/D ratio, and significantly correlated with a poorer prognosis (P ¼ 0.0186). Moreover, the high C/D ratio was found to be an independent prognostic factor on multivariate analysis (P ¼ 0.0266; hazard ratio 5.988). CONCLUSION: Prediction of CCND1 amplification using plasma DNA is thought to be a promising prognostic biomarker in ESCC patients.

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Amplification of the EGF receptor and c‐myc genes in human esophageal cancers

Cited by 124 publications

References 19 publications

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Expression of esophageal cancer related gene 4 (ECRG4), a novel tumor suppressor gene, in esophageal cancer and its inhibitory effect on the tumor growth in vitro and in vivo

Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma

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