Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three human leucine-rich repeats and immunoglobulin-like domains (LRIG1-3) genes and proteins have recently been characterized. LRIG1 has been shown to be a suppressor of tumor growth by counteracting the signaling of epidermal growth factor receptor (EGFR) family members, including EGFR (ERBB1). Expression of LRIG proteins seems to be of importance in the pathogenesis of astrocytic tumors. In this study, the expression of LRIG1-3 was evaluated in 51 human ependymomas by immunohistochemistry. LRIG proteins were detected in all ependymomas analyzed, however, with a pronounced heterogeneity in expression and subcellular localization. Higher cytoplasmic immunoreactivity of LRIG1 correlated with older patient age and higher LRIG1 nuclear immunoreactivity with lower WHO Grade. LRIG1 displayed a stronger immunoreactivity in the cytoplasm and nuclei in spinal ependymomas than in the posterior fossa or supratentorial ependymomas, while perinuclear LRIG3 was more highly expressed in supratentorial than in infratentorial ependymomas. The indications that expression and subcellular localization of LRIG proteins could be pathogenetically associated with specific clinicopathological features of ependymoma tumors might be of importance in the carcinogeneses and tumor progression of human ependymomas.
 ...
PMID:Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age. 1921 16

Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
 ...
PMID:A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk. 2044 91

Evidences of a crosstalk between Epidermal Growth Factor Receptor (EGFR) and Glucocorticoid Receptor (GR) has been reported, ranging from the modulation of receptor levels or GR mediated transcriptional repression of EGFR target genes, with modifications of epigenetic markers. The present study focuses on the involvement of EGFR positive and negative feedback genes in the establishment of cetuximab (CTX) resistance in metastatic Colorectal Cancer (CRC) patients. We evaluated the expression profile of the EGFR ligands TGFA and HBEGF, along with the pro-inflammatory cytokines IL-1B and IL-8, which were previously reported to be negatively associated with monoclonal antibody response, both in mice and patient specimens. Among EGFR negative feedback loops, we focused on ERRFI1, DUSP1, LRIG3, and LRIG1. We observed that EGFR positive feedback genes are increased in CTX-resistant cells, whereas negative feedback genes are reduced. Next, we tested the expression of these genes in CTX-resistant cells upon GR modulation. We unveiled that GR activation leads to an increase in ERRFI1, DUSP1, and LRIG1, which were shown to restrict EGFR activity, along with a decrease in the EGFR activators (TGFA and IL-8). Finally, in a cohort of xenopatients, stratified for response to cetuximab, we observed an inverse association between the expression level of LRIG1 and CRC progression upon CTX treatment. Our model implies that combining GR modulation to EGFR inhibition may yield an effective treatment strategy in halting cancer progression.
 ...
PMID:Glucocorticoid Receptor Modulates EGFR Feedback upon Acquisition of Resistance to Monoclonal Antibodies. 3105 57