Prognostic significance of epidermal growth factor receptor in esophageal squamous cell carcinomas

Ozawa, Soji; Ueda, Mitsuharu; Ando, Nobutoshi; Shimizu, Nobuyoshi; Abe, Osahiko

doi:10.1002/1097-0142(19890601)63:11<2169::aid-cncr2820631117>3.0.co;2-w

Cited by 171 publications

(68 citation statements)

References 15 publications

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“…In particular, we and others have recently reported that the overexpression of EGFR of oesophageal SCC, partially accounted for by gene amplification, is found in 50 -70% (Itakura et al, 1994;Hanawa et al, 2006), and is indicative of a poor prognosis (Ozawa et al, 1989;Yano et al, 1991). Moreover, we showed that the overexpression of HER-2 in oesophageal SCC was found in 30.3% (Mimura et al, 2005b).…”

supporting

confidence: 67%

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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supporting

confidence: 67%

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

et al. 2007

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“…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). Thus, the mitogenic and anti-apoptotic signals transduced from EGF receptors may play a very important role in the growth and prognosis of human esophageal carcinomas.…”

Section: Discussionmentioning

confidence: 98%

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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“…This study and others have demonstrated that esophageal squamous cell carcinoma cells express higher levels of EGFR and HER2 compared with other types of malignant cells (18,20). In addition, a correlation between EGFR expression and prognosis of esophageal cancer has also been reported (19). Therefore, this may suggest that targeting therapies against EGFR and HER2 may be promising for esophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In esophageal squamous cell carcinoma, there is frequent overexpression of EGFR and a correlation between EGFR expression and prognosis has also been reported (18,19). In addition, HER2 expression is detectable in a variety of esophageal tumors (20).…”

Section: Introductionmentioning

confidence: 99%

The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

Ako

Yamashita²,

Ohira³

et al. 2007

Oncol Rep

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Abstract. The epidermal growth factor receptor (EGFR) is a member of the EGFR family of receptors. EGFR and other members of the EGFR family have been shown to play significant roles in human cancer cell proliferation and therefore present important molecular targets for the treatment of cancer. The purpose of this study was to examine the effect of the pan-erbB tyrosine kinase inhibitor CI-1033 against esophageal squamous cell carcinoma in vitro and in vivo. We selected 4 human esophageal squamous cell carcinoma cell lines (TT, TE2, TE6, and TE10), and determined their expression of EGFR and HER2. We examined the ability of CI-1033 to inhibit cell growth in vitro and in vivo. EGFR and HER2 were overexpressed in all 4 esophageal cancer cells. We found that CI-1033 could inhibit the growth of esophageal cancer cell lines in a dose-dependent manner with the inhibition of phosphorylation of both MAPK and AKT. The oral administration of CI-1033 exerted a significant antitumor effect on esophageal cancer tumors in athymic nude mice. Our results suggest that CI-1033 effectively inhibits the growth of esophageal squamous cell carcinoma which co-expresses both EGFR and HER2 with the inhibition of phosphorylation of both MAPK and AKT. Furthermore, in vivo animal studies of CI-1033 suggest that CI-1033 holds significant clinical potential in esophageal cancer.

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Prognostic significance of epidermal growth factor receptor in esophageal squamous cell carcinomas

Cited by 171 publications

References 15 publications

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

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

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

The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

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