scholarly journals Phosphatidylinositol-4-phosphate 5-Kinase-1β Is Essential for Epidermal Growth Factor Receptor-mediated Endocytosis

2001 ◽  
Vol 276 (50) ◽  
pp. 47212-47216 ◽  
Author(s):  
M. Alejandro Barbieri ◽  
Colin M. Heath ◽  
Elizabeth M. Peters ◽  
Alan Wells ◽  
J. Nathan Davis ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Membrane Trafficking ◽  
Growth Factor Receptor ◽  
Receptor Internalization ◽  
Receptor Mediated Endocytosis ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Phosphatidylinositol 4

Phosphatidylinositol-4,5-bisphosphate (PIP2) is known to play an important role in signal transduction and membrane trafficking. We show that one enzyme responsible for PIP2production, phosphatidylinositol-4-phosphate 5-kinase type 1β (PIPKβ), is essential for epidermal growth factor receptor (EGFR)-mediated endocytosis. Expression of murine PIPKβ in NR6 cells expressing EGFR strikingly increased receptor internalization. Moreover, the kinase was shown to form an immunoprecipitable complex with EGFR. Expression of either a truncated kinase or a kinase dead mutant inhibited EGFR endocytosis and also blocked the membrane recruitment of PIPKβ and both clathrin light chain and dynamin. Our results delineate a novel mechanism by which PIPKβ regulates receptor-mediated endocytosis and receptor tyrosine kinase membrane traffic.

scholarly journals Epidermal growth factor receptor protein expression in lung cancer and survival analysis

2018 ◽  
Vol 5 (3) ◽  
pp. 550
Author(s):  
Shivalingaswamy Salimath ◽  
Jayaraj B. S. ◽  
Mahesh P. A. ◽  
M. D. Majeed Pasha ◽  
Lokesh K. S. ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Multivariate Analysis ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Nsclc Patients

Background: Epidermal Growth Factor Receptor (EGFR) is one of the important molecules involved in lung cancer initiation and progression. Studies on over expression of EGFR and its survival in relation with Non-small cell lung cancer (NSCLC) patients have yielded controversial results. Prevalence of EGFR expression in NSCLC patients and 6-month survival in south Indian population is unknown.Methods: We carried out a prospective study in tertiary hospital. Diagnosed patients with NSCLC were included in the study and were interviewed with questionnaire containing demography and investigations like Chest X-ray, CT thorax, Bronchoscopy were recorded. EGFR expression analysis was done for all patients and were followed up monthly for 6 months and details of survival and treatment were collected. Cox regression analysis was used to assess their survival.Results: 50 patients with NSCLC were included. Forty-four (88%) were men, median age of study group was 65 years. Twenty-seven patients (54%) had Adenocarcinoma, 14 patients (28%) had Squamous cell carcinoma, 7 patients (14%) had poorly differentiated carcinoma and 2 patients (4%) had large cell carcinoma. Thirty-four (68%) samples were positive for EGFR expression. On multivariate analysis we found patients who took chemotherapy and with good performance status (Karnofsky score >65 and Eastern Cooperative Oncology Group >2.5) had better survival at 6 months.Conclusions: Patients with EGFR positivity had better survival with chemotherapy but worse with radiotherapy. Patients who took chemotherapy and had good performance status had better survival on multivariate analysis. We didn’t find any correlation between EGFR positivity and poor survival.

scholarly journals Inhibition of epidermal growth factor receptor (EGFR) expression by human cytomegalovirus correlates with an increase in the expression and binding of Wilms' Tumour 1 protein to the EGFR promoter

2009 ◽  
Vol 90 (7) ◽  
pp. 1569-1574 ◽  
Author(s):  
Insiya Jafferji ◽  
Mark Bain ◽  
Christine King ◽  
John H. Sinclair
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Human Cytomegalovirus ◽  
Growth Factor Receptor ◽  
Cell Surface Receptor ◽  
Wilms Tumour ◽  
Promote Cell Proliferation ◽  
Egfr Expression ◽  
Epidermal Growth

Infection with human cytomegalovirus (HCMV) modulates the expression of a number of cellular receptors and is known to inhibit expression of the epidermal growth factor receptor (EGFR), a cell surface receptor that can promote cell proliferation through a cascade of intracellular signalling events. We have examined the mechanisms by which HCMV mediates downregulation of EGFR expression and show that virus infection results in the profound upregulation of Wilms' Tumour 1 (WT1) protein, a transcription factor associated with the negative regulation of a number of growth factors and growth factor receptors, including EGFR. Moreover, chromatin immunoprecipitation experiments also show that HCMV infection results in increased binding of WT1 to the EGFR promoter. Finally, we show that depleting the cell of WT1 using small interfering RNA abrogates virus-mediated downregulation of EGFR. Taken together, our observations suggest that HCMV-mediated repression of EGFR expression results from a virus-mediated increase in cellular WT1, a known pleiotropic regulator of mitogenesis, apoptosis and differentiation.

Phase II Study of Erlotinib in Patients With Advanced Biliary Cancer

2006 ◽  
Vol 24 (19) ◽  
pp. 3069-3074 ◽  
Author(s):  
Philip A. Philip ◽  
Michelle R. Mahoney ◽  
Cristine Allmer ◽  
James Thomas ◽  
Henry C. Pitot ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Skin Rash ◽  
Group Performance ◽  
Growth Factor Receptor ◽  
Locoregional Therapy ◽  
Biliary Cancer ◽  
Egfr Expression ◽  
Epidermal Growth

Purpose Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months. Methods Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally. Results Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash. Conclusion Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.

A Conjugate of an Anti-Epidermal Growth Factor Receptor (EGFR) VHH and a Cell-Penetrating Peptide Drives Receptor Internalization and Blocks EGFR Activation

ChemBioChem ◽  
2017 ◽  
Vol 18 (24) ◽  
pp. 2390-2394 ◽  
Author(s):  
Sanne A. M. van Lith ◽  
Dirk van den Brand ◽  
Rike Wallbrecher ◽  
Sander M. J. van Duijnhoven ◽  
Roland Brock ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Internalization ◽  
Cell Penetrating Peptide ◽  
Egfr Activation ◽  
Cell Penetrating ◽  
A Cell ◽  
Epidermal Growth
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