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1.
目的探讨酪氨酸激酶抑制剂(Tyrosine kinase inhibitor,TKI)对培养气管上皮细胞生长的影响.方法通过MMT法、3H-胸腺嘧啶(3H-TdR)掺入法及流式细胞计数,观察3种TKIs:Tyrphostin AG1478、Genistein(Sigma)及金转停对原代培养的大鼠气管上皮细胞增殖、周期及凋亡的影响,以及TKIs对表皮生长因子(EGF)的阻断作用.结果MTT法显示3种TKI均对气管上皮细胞的生长具有时间和剂量依赖性抑制作用,同时,TKI阻断EGF对气管上皮细胞生长的刺激作用,3种TKIs的作用无明显差异;1μmol/L的Tyrphostin AG1478、Genistein及金转停分别使气管上皮细胞的TdR掺入率降低18.3%、20.9%及19.7%,与MTT比色法结果一致.同时,Tyrphostin AG1478不仅加速气管上皮细胞的凋亡而且阻止细胞有丝分裂.TKIs可阻断表皮生长因子(EGF)对气管上皮细胞生长的刺激作用.结论TKIs不仅抑制对原代培养的大鼠气管上皮细胞的生长,加速其凋亡,而且可阻断EGF对气管上皮细胞生长的刺激作用,3种抑制剂的作用无明显差异. 相似文献
2.
Pelosi G Scarpa A Veronesi G Spaggiari L Del Curto B Moore PS Maisonneuve P Sonzogni A Masullo M Viale G 《Virchows Archiv : an international journal of pathology》2005,447(6):969-977
Nuclear translocation of β-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation
in nonsmall cell lung cancer. Less is known on β-catenin transactivation in high-grade pulmonary neuroendocrine tumors and
on the status of β-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or β-catenin target genes
cyclin D1 and matrix metalloproteinase-7 (MMP-7). β-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine
carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for β-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. β-catenin was
expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed
immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining
along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated
with EGFR and HER-2 protein expression. β-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and
two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These
cases, however, did not show β-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear β-catenin and
any clinicopathological variable including patients' survival. The subcellular compartmentalization of β-catenin is profoundly
altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows β-catenin nuclear accumulation
in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification
or expression.
The authors have no significant financial or other relationship with the manufacturers of any commercial products or commercial
services presented in this paper 相似文献
3.
The canine's olfactory acuity is legendary, but neither its main olfactory system nor its vomeronasal system has been described in much detail. We used immunohistochemistry on paraffin-embedded sections of male and female adult dog vomeronasal organ (VNO) to characterize the expression of proteins known to be expressed in the VNO of several other mammals. Basal cell bodies were more apparent in each section than in rodent VNO and expressed immunoreactivity to anticytokeratin and antiepidermal growth factor receptor antibodies. The thin layer of neurone cell bodies in the sensory epithelium and axon fascicles in the lamina propria expressed immunoreactivity to neurone cell adhesion molecule, neurone-specific beta tubulin and protein gene product 9.5. Some neurones expressed growth-associated protein 43 (GAP43): and a number of those also expressed neurone-specific beta tubulin-immunoreactivity. Some axon fascicles were double labelled for those two proteins. The G-protein alpha subunits Gi and Go, involved in the signal transduction pathway, showed immunoreactivity in the sensory cell layer. Our results demonstrate that the canine vomeronasal organ contains a population of cells that expresses several neuronal markers. Furthermore, GAP43 immunoreactivity suggests that the sensory epithelium is neurogenic in adult dogs. 相似文献
4.
Aims : To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.
Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.
Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours. 相似文献
Methods and results
Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.
Conclusion
Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours. 相似文献
5.
孕期四氯二苯对二噁英处理对子鼠颌下腺表皮生长因子和表皮生长因子受体的影响 总被引:1,自引:0,他引:1
目的 研究孕期四氯二苯对二噁英(TCDD)处理对子鼠颌下腺表皮生长因子(EGF)和表皮生长因子受体(EGFR)的影响。方法 孕15d大鼠给予TCDD(5μg/kg)灌胃1次,采用免疫组织化学方法,对不同发育阶段的子鼠颌下腺进行了观察。结果 在PND32,PND49d,TCDD组颌下腺EGF和EGFR的免疫反应阳性产物比对照组丰富,有显著性差异。结论 孕期TCDD暴露促进了青春期和青春前期子鼠颌下腺EGF的生成和EGFR的表达。 相似文献
6.
The canine's olfactory acuity is legendary, but neither its main olfactory system nor its vomeronasal system has been described in much detail. We used immunohistochemistry on paraffin-embedded sections of male and female adult dog vomeronasal organ (VNO) to characterize the expression of proteins known to be expressed in the VNO of several other mammals. Basal cell bodies were more apparent in each section than in rodent VNO and expressed immunoreactivity to anticytokeratin and antiepidermal growth factor receptor antibodies. The thin layer of neurone cell bodies in the sensory epithelium and axon fascicles in the lamina propria expressed immunoreactivity to neurone cell adhesion molecule, neurone-specific beta tubulin and protein gene product 9.5. Some neurones expressed growth-associated protein 43 (GAP43): and a number of those also expressed neurone-specific beta tubulin-immunoreactivity. Some axon fascicles were double labelled for those two proteins. The G-protein alpha subunits Gi and Go, involved in the signal transduction pathway, showed immunoreactivity in the sensory cell layer. Our results demonstrate that the canine vomeronasal organ contains a population of cells that expresses several neuronal markers. Furthermore, GAP43 immunoreactivity suggests that the sensory epithelium is neurogenic in adult dogs. 相似文献
7.
Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow 总被引:7,自引:3,他引:7
Cabioglu N Sahin A Doucet M Yavuz E Igci A O Yildirim E Aktas E Bilgic S Kiran B Deniz G Price JE 《Clinical & experimental metastasis》2005,22(1):39-46
Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK+ cells was 236 (range, 20–847) per 5 × 104 enriched BM cells. The presence of CK+ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK+ per 5 × 104 enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow. 相似文献
8.
目的 探讨能否直接利用肿瘤细胞膜进行表皮生长因子受体 (Epidermalgrowthfactorreceptor,EGFR)催化活性检测。方法 首先筛选出EGFR基因表达水平相对较高的细胞株MDA MB 2 31,通过差速离心制备细胞膜 ,采用Westernblotting检测EGFR催化磷酸化的程度。结果 底物被磷酸化 ,加入特异性拮抗剂AG14 78后 ,磷酸化被抑制。结论 利用肿瘤细胞膜检测EGFR活性的设想是成立的 ,并且其方法简便、经济。 相似文献
9.
目的研究喉癌中表皮生长因子受体(EGFR)基因的扩增、表达,探讨其在喉癌发生、发展中的作用及临床意义。方法采用差异PCR(differential PCR)方法检测40例喉鳞状细胞癌及配对癌旁正常组织中EGFR基因的扩增(即基因拷贝数增加);应用RT-PCR方法检测EGFR mRNA水平;应用SPSS13.0软件对数据进行统计学分析。结果喉癌组织中有13例(占32.5%)EGFR基因拷贝数增加,癌旁对照组中则未检测到(χ2=15.537,P<0.005);喉癌组织中EGFR mRNA平均积分光密度为872.356±62.340,癌旁对照组为346.425±57.380(t=5.959,P<0.001);喉癌组织分化程度越低,病理分期越晚,EGFR基因扩增和mRNA表达水平越高(P<0.05)。结论喉癌中EGFR基因在DNA水平上的扩增是EGFR mRNA过表达的原因之一,EGFR的扩增和过表达在喉癌的发生、进展中发挥一定作用。 相似文献
10.
Clemens B. M. Kienhuis Mels Sluyser Cees C. J. de Goeij Paul G. Koenders Theo J. Benraad 《Breast cancer research and treatment》1993,26(3):289-295
Summary Twenty-six serially transplanted Grunder (GR) strain mouse mammary tumors were analyzed for epidermal growth factor receptor (EGFR) and EGFR-ligand levels, in addition to steroid hormone receptors (estrogen receptor, ER, progesterone receptor, PgR). In concordance with earlier studies, hormone dependent (HD) and hormone responsive (HR) tumors were found to be positive for both ER and PgR, whereas hormone independent (HI) tumors contained only 30% of the ER concentration that was found in the HD tumors. PgR was undetectable in HI tumors. HI tumors contained 2.5 to 3-fold higher EGFR levels than HD/HR tumors, an observation which shows remarkable concordance with studies on EGFR in human breast cancer. On the other hand, the level of EGFR-ligand(s) was positively associated with ER levels and was three-fold higher in HD/HR tumors than in HI tumors. The low EGFR in HD/HR tumors relative to HI tumors may be the result of downregulation by EGFR ligands produced under ER control. During progression to hormone independence this downregulation of EGFR is then abolished in absence of ER. The increase in EGFR may therefore be a secondary effect rather than a key event in the progression to hormone independence in this mouse mammary tumor model.Abbreviations EGF
Epidermal Growth Factor
- EGFR
Epidermal Growth Factor Receptor
- ER
Estrogen Receptor
- PgR
Progesterone Receptor
- HD
Hormone Dependent
- HR
Hormone Responsive
- HI
Hormone Independent
- HAP
Hydroxylapatite
- DCC
Dextran Coated Charcoal
- GR
Grunder
- TGF-
Transforming Growth Factor- 相似文献