EGFR blockade by tyrosine kinase inhibitor or monoclonal antibody inhibits growth, directs terminal differentiation and induces apoptosis in the human squamous cell carcinoma HN5.

Modjtahedi, Helmout; Affleck, Karen; Stubberfield, Colin R.; Dean, C

doi:10.3892/ijo.13.2.335

Cited by 43 publications

(39 citation statements)

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“…7). Previously, evidence indicated that EGFR blockade leads to the observed increase in tumor cell apoptosis (26)(27)(28). Our findings, that the inducing of apoptosis within tumor cells is through the blocking of EGFR, coincide with previous studies (26)(27)(28).…”

Section: Discussionsupporting

confidence: 80%

“…Our findings, that the inducing of apoptosis within tumor cells is through the blocking of EGFR, coincide with previous studies (26)(27)(28). by directing terminal differentiation (26,29,30). These studies also provided evidence for a relationship between the in vivo antitumor activity of xenogeneic homologous induced IgG and their capacity to induce differentiation of cancer cells.…”

Section: Discussionsupporting

confidence: 79%

See 1 more Smart Citation

Humoral immunity responses against EGFR-positive tumor cells induced by xenogeneic EGFR expressed in the yeast Pichia pastoris

Fang

Chen²,

Chen³

et al. 1998

Int J Mol Med

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Abstract. The breaking of immune tolerance against self epidermal growth factor receptor (EGFR) should be a promising approach for the treatment of those receptorpositive tumors. We have previously shown that human EGFR as a xenoantigen induced a specific antitumor activity against EGFR-positive mouse tumors. Our further studies demonstrated that a recombinant form of extracellular domain of mouse EGFR provoked active cellular immunity responses against EGFR-positive human tumors. In this study, we investigated whether the recombinant murine EGFR expressed in the yeast Pichia pastoris would induce humoral immunity responses against EGFR-positive human tumors. To test this concept, polyclonal immunoglobulin (IgG), which was produced by vaccinating the rabbits with the recombinant mEGFR, was purified from the sera of the rabbits. We evaluated the antitumor activity of the polyclonal IgG in the nude mice bearing A431 tumors. Mice were i.v. treated with the purified IgG at 100 mg/kg 1 day before the mice were inoculated with the tumor cells and then twice per week for 4 weeks. Our results showed that the polyclonal IgG would efficiently inhibit the growth of the solid tumor in vivo. The antitumor effect of the polyclonal IgG may result from the increasing rate of apoptosis and induction of differentiation of the tumor cells in vivo. The present findings may provide insight into treatment of EGFRpositive tumors through induction of the humoral immunity responses based on xenogeneic homologous EGFR.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 79%

Humoral immunity responses against EGFR-positive tumor cells induced by xenogeneic EGFR expressed in the yeast Pichia pastoris

Fang

Chen²,

Chen³

et al. 1998

Int J Mol Med

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“…The results showed that only BACE activity was increased by RTK stimulation in a time-dependent manner ( Figure 1A, 1C) while BACE expression was not affected (Supplement 1, Figure B); and a-and γ-secretase activities were not significantly affected. This enhancement of BACE activity was completely blocked by antibodies against EGFR [35] or NGFR [36] respectively ( Figure 1A, 1C). These data indicated that the observed enhancement in BACE activity was dependent on the activation of the corresponding RTK.…”

Section: Stimulation Of Rtk Increases Bace Activity and Aβ Productionmentioning

confidence: 92%

Receptor tyrosine kinases positively regulate BACE activity and Amyloid-β production through enhancing BACE internalization

et al. 2007

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Amyloid-β (Aβ) peptide, the primary constituent of senile plaques in Alzheimer's disease (AD), is generated by β-secretase-and γ-secretase-mediated sequential proteolysis of the amyloid precursor protein (APP). The aspartic protease, β -site APP cleavage enzyme (BACE), has been identified as the main β-secretase in brain but the regulation of its activity is largely unclear. Here, we demonstrate that both BACE activity and subsequent Aβ production are enhanced after stimulation of receptor tyrosine kinases (RTKs), such as the receptors for epidermal growth factor (EGF) and nerve growth factor (NGF), in cultured cells as well as in mouse hippocampus. Furthermore, stimulation of RTKs also induces BACE internalization into endosomes and Golgi apparatus. This enhancement of BACE activity and Aβ production upon RTK activation could be specifically inhibited by Src family kinase inhibitors and by depletion of endogenous c-Src with RNAi, and could be mimicked by over-expressed c-Src. Moreover, blockage of BACE internalization by a dominant negative form of Rab5 also abolished the enhancement of BACE activity and Aβ production, indicating the requirement of BACE internalization for the enhanced activity. Taken together, our study presents evidence that BACE activity and Aβ production are under the regulation of RTKs and this is achieved via RTK-stimulated BACE internalization, and suggests that an aberration of such regulation might contribute to pathogenic Aβ production.

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“…Epidermal growth factor receptor-associated protein tyrosine kinase complexes also have vital antiapoptotic functions in human breast cancers (Modjtahedi et al, 1998;Witters et al, 1999) and the blockade of EGFR not only adversely affected cell growth, but also showed a sign of terminal differentiation and induces apoptosis in the human cancer cells (Modjtahedi et al, 1998). Similarly, druginduced apoptosis in human breast cancer cells was abrogated by using EGFR antisense RNA (Dixit et al, 1997), suggesting that a critical level of EGFR signalling, which is amplified in some common cancers, may be necessary for DNA-damaging drugmediated apoptosis in tumour cells and suggest an inhibitory effect of this pathway on the repair of cisplatin-damaged DNA.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the treatment of cancer cells with EGFR tyrosine kinase inhibitor markedly potentiates the efficacy of many cytotoxic agents against several human cancer xenografts (She et al, 2003). The use of antisense oligonucleotides or monoclonal antibodies to EGFR also showed significant inhibition of cancer cell growth (Modjtahedi et al, 1998;Witters et al, 1999), while activation of EGFR family members suppresses the cytotoxic effects of TNF-alpha (Hoffmann et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Lack of EGF receptor contributes to drug sensitivity of human germline cells

et al. 2005

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Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours.

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EGFR blockade by tyrosine kinase inhibitor or monoclonal antibody inhibits growth, directs terminal differentiation and induces apoptosis in the human squamous cell carcinoma HN5.

Cited by 43 publications

References 0 publications

Humoral immunity responses against EGFR-positive tumor cells induced by xenogeneic EGFR expressed in the yeast Pichia pastoris

Humoral immunity responses against EGFR-positive tumor cells induced by xenogeneic EGFR expressed in the yeast Pichia pastoris

Receptor tyrosine kinases positively regulate BACE activity and Amyloid-β production through enhancing BACE internalization

Lack of EGF receptor contributes to drug sensitivity of human germline cells

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