Genistein is a high specific and noncompetitive inhibitor of epidermal growth factor receptor tyramine kinase domain (EGFR-TK). In the paper, a molecular docking between genistein and EGFR-TK was studied to explore the mechanism of their interaction and antitumor mechanism of genistein by AUTODOCK 3.05 program. The results indicated that genistein located in the active cavity of EGFR-TK by high affinity (deltaG = -31.2 kJ/mol), and genistein inhibited EGFR-TK by interfering with forming of Lys721/Glu738 ion pair. The inhibition belonged to noncompetitive interaction, in which hydrophobic force and hydrogen bond played key roles.
Catalytic Domain ; Genistein ; metabolism ; pharmacology ; Models, Molecular ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; metabolism

Non-small cell lung cancer is one of the leading causes of all cancer deaths, but despite years of research, it is still difficult to predict the response and clinical outcome of the disease. In recent years, new treatment strategies targeting the epidermal growth factor receptors (EGFR) have been developed. EGFR is one of the most frequently over expressed proteins in various cancers, including lung cancer, and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments. Therefore, EGFR has become an attractive target for various treatment strategies. However, it is important to note that not all patients with lung cancer are suitable for targeted treatment, and that patients should be selected for this treatment. Several studies have proven that the status of the EGFR can be both an indicator of suitability for treatment with, and predict the likelihood of response to EGFR targeted therapy. There are many standard techniques to be used for the detection of EGFR. This overview summarizes the ongoing and future investigations to determine the status of the EGFR.
Carcinoma, Non-Small-Cell Lung ; blood ; metabolism ; Humans ; Receptor, Epidermal Growth Factor ; blood ; metabolism

Psoriasis is characterized by disregulation of keratinocyte growth with profound epidermal hyperplasia. Keratinocyte hyperplasia in psoriasis may be expained in part by overproduction of growth factor, and by altered metabolism of the epidemal growth factor receptors (EGFR) in affected skin. The expression of epidermal growth f ictor receptor was investigated by Northern blot and slot-blot analysis of total RNA extrated from biopsies of normal skin and psoriatic lesions. In Northern blot analysis, EGFR-specific mRNA transcripts from psoriatic tissues demonstrated the specificity of hybridizarion with a EGFR mDNA probe. The size of EGFR mRNA transcript was 6.7kb in psoriasis lesions which showed no change of quality. In slot-blot analysis, the levels of EGFR mRNA in poriasis revealed a 1.2 fold to 4.1 fold elevation when compared to normal skin. EGFR were present in all epidermal layers by immunoperoxidase staining, whereas in normal skin they were primarily present in the stratum basalis. These results indicate that the increased expresion of the EGFR gene may be, in part, responsible for the hyperproliferation of the epider nis and that retained EGFR may reflect incomplet; abnormal differentiation in active porasis. This altered process of EGFR metabolism may be involved in the pathogenesis of psoriasis.
Biopsy ; Blotting, Northern ; Epidermal Growth Factor* ; Genes, erbB-1 ; Hyperplasia ; Keratinocytes ; Metabolism ; Psoriasis* ; Receptor, Epidermal Growth Factor* ; Receptors, Growth Factor ; RNA ; RNA, Messenger ; Sensitivity and Specificity ; Skin

OBJECTIVETo elucidate the regulation of the phosphorylation of epidermal growth factor receptor (EGFR) by the EB virus encoded latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma cell line.

METHODSThe levels of EGFR expression and phosphorylation in pTet-on LMP1 HNE2 cell, a nasopharyngeal carcinoma (NPC) cell line, in the dynamic expression of LMP1 induced by different concentrations of doxycycline (Dox) were observed. The EGFR dominant negative mutant and LMP1 antisense expression plasmid were transiently transfected into pTet-on LMP1 HNE2 cells by lipofectamine, and the changes in EGFR phosphorylation were observed by immunocoprecitation and Western blot. The changes in EGFR phosphorylation were observed after EGF treatment.

RESULTSIn pTet-on LMP1 HNE2 cells, Dox-induced LMP1 upregulated EGFR expression and phosphorylation in a dose-dependent manner. After EGFR dominant negative mutant was transfected into pTet-on LMP1 HNE2 cells, the increase of EGFR phosphorylation was inhibited completely. When LMP1 antisense expression plasmid was transfected into pTet-on LMP1 HNE2 cells, the levels of EGFR phosphorylation were also inhibited significantly. Meanwhile, after EGF had been added into pTet-on LMP1 HNE2 cells, increase of EGFR phosphorylation was induced, but it was completely blocked by EGFR dominant negative mutant and the introduction of LMP1 antisense.

CONCLUSIONEB virus encoded LMP1 not only induces the dose-dependent expression of EGFR, but also the dose-dependent phosphorylation of EGFR. The phosporylation of EGFR may play a vital role in the development of nasopharyngeal carcinoma.

Blotting, Western ; Epidermal Growth Factor ; metabolism ; Herpesvirus 4, Human ; metabolism ; Humans ; Nasopharyngeal Neoplasms ; pathology ; virology ; Phosphorylation ; Receptor, Epidermal Growth Factor ; metabolism ; Tumor Cells, Cultured ; Viral Matrix Proteins ; metabolism

OBJECTIVETo explore the relationship between substance P (SP) released from peripheral nerve endings and the expression of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) during wound healing.

METHODSFifty Wistar rats were randomly divided into 2 groups, injury group and capsaicin group. In the injury group, a full-thickness skin wound on the back of the rat was taken. The wound edge and granulation tissues were taken on the 1st, 3rd, 6th, 9th, 12th days after injury, respectively. In the capsaicin group, capsaicin was injected subcutaneously on the back of the rats to destroy the sensory nerve to prevent the secretion of SP, then a wound and sample was made in the same way. Immunohistochemistry and in situ hybridization were employed to detect the expression of SP, EGF/EGFR, and EGF mRNA/EGFR mRNA in the granulation tissues.

RESULTSIn the injury group, immunohistochemical stain of SP and EGF/EGFR was located on the hair follicles and sebaceous glands at the 1st day. And the stain of SP was obvious at the 3rd day in the granulation tissues, then decreased gradually. EGF/EGFR was at low level at the 3rd day, then increased gradually and reached the peak at the 9th day, then declined. In the capsaicin group, the immunohistochemical stain of SP and EGF/EGFR was faint and without obvious change during the wound healing process. The tendency of the EGF mRNA/EGFR mRNA expression was similar to that of EGF/EGFR.

CONCLUSIONSDuring wound healing, SP may promote the healing process by affecting the expression of EGF/EGFR in the granulation tissues.

Animals ; Epidermal Growth Factor ; metabolism ; Granulation Tissue ; metabolism ; Immunohistochemistry ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, Epidermal Growth Factor ; metabolism ; Substance P ; physiology ; Wound Healing ; physiology

Breast Neoplasms ; metabolism ; Female ; Humans ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo build 3D-pharmacophore model of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors using distance comparisons method and design novel EGFR inhibitors.

METHODSThirteen typical EGFR inhibitors were selected, and their biologically active conformations were obtained by using DOCK5.0 program, then 3D-pharmacophore model of EGFR inhibitors was built using distance comparisons method.

RESULTSValidation of the 3D-pharmacophore model was carried out and novel structures with potential inhibitory activity were selected by means of 3D-searching and docking method.

CONCLUSIONThis method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.

Drug Design ; Enzyme Inhibitors ; Epidermal Growth Factor ; metabolism ; Models, Chemical ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; chemistry ; Structure-Activity Relationship

OBJECTIVETo investigate the epidermal growth factor(EGF) and epidermal growth factor receptor(EGFR) expression in atrophic gastritis in rats to explore the relationship between EGF and chronic atrophic gastritis(CAG).

METHODSThe serum EGF and gastric mucosal, EGFR level were measured in 20 rats with CAG and 20 normal controls.

RESULTSThe average EGF level (0.149+/-0.020) microg/L and 80% positive rate of EGFR expression observed in CAG group were significantly higher than those in control group[(0.043+/-0.003) microg/L and 0%,P<0.01].

CONCLUSIONThe study demonstrates an association of high levels of EGF and positive EGFR expression in CAG rats. Further studies are necessary to clarify whether EGF/EGFR play a significant role in the pathogenesis of CAG.

Animals ; Epidermal Growth Factor ; blood ; physiology ; Gastric Mucosa ; chemistry ; Gastritis, Atrophic ; drug therapy ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Epidermal Growth Factor ; analysis ; physiology

Animals ; Blotting, Western ; Epidermal Growth Factor ; analysis ; Female ; Ischemia ; physiopathology ; Kidney ; embryology ; metabolism ; Models, Animal ; Pregnancy ; Rats ; Rats, Wistar ; Receptor, Epidermal Growth Factor ; analysis ; Uterus ; blood supply

OBJECTIVETo evaluate the expression of the type I growth factor receptor family [epidermal growth factor receptor (EGFR), ErbB2 and ErbB3] by the epithelial cells in pterygium.

METHODSImmunoflourescent staining and Western blotting were performed to detect the expression pattern and quantity of EGFR, ErbB2 and ErbB3 proteins in the epithelia of 15 patients with primary pterygium and 12 subjects with normal conjunctiva.

RESULTSIn immunofluorescent staining, the EGFR protein was present in the basal cells while the ErbB2 and ErbB3 were expressed by the superficial cells in normal conjunctival epithelium. Of the pterygium cases 15, 11 were stained by EGFR, ErbB2 and ErbB3 in the full thickness of the epithelium and showed stronger staining compared with the control group. Four of them showed a similar staining pattern to the normal conjunctiva group. The density of protein bands detected by Western blotting for all three growth factor receptors was consistent with the immunofluorescent staining. Compared with normal conjunctiva, stronger protein bands of these three receptors were found in all of the pterygium specimens, in which EGFR, ErbB2 and ErbB3 were expressed in the full thickness, as shown by immunofluorescent staining.

CONCLUSIONSThe increased expression of EGFR, ErbB2 and ErbB3 proteins was present in pterygium, which indicated that pterygium is a disorder with abnormal proliferation. The abnormal expression of EGFR, ErbB2 and ErbB3 by the epithelium and the communication with cytokines in the stroma in pterygium may be a key pathogenic factor in this disorder.

Adult ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pterygium ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism