Comparative Genomic Sequence Analysis and Isolation of Human and Mouse Alternative EGFR Transcripts Encoding Truncated Receptor Isoforms

Reiter, Jill L.; Threadgill, David W.; Eley, Greg; Strunk, Karen E.; Danielsen, Andrew J.; Sinclair, Colleen; Pearsall, R. Scott; Green, Patricia J.; Yee, Della; Lampland, Andrea L.; Balasubramaniam, Swarna; Crossley, Tonia D.; Magnuson, Terry; James, C. David; Maihle, Nita J.

doi:10.1006/geno.2000.6341

Cited by 96 publications

(114 citation statements)

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“…Gene therapy targeting TK domain in glioma therapy EGFR gene consists of 28 exons and encodes a 170 kDa of glycoprotein, comprising an extracellular region (encoded by exons 1-16), a membrane spanning region (encoded by exon 17) and an intracellular region (encoded by exons [18][19][20][21][22][23][24][25][26][27][28]. 19 The extracellular portion of EGFR is Figure 5 Compare to the group of PBS and psiRNA-scr, tumor growth in nude mice in the group of psiRNA-EGFR and panti-EGFR were inhibited (Po0.001) (a), EGFR expression of tumors was downregulated (b), GFAP expression was upregulated (c), apoptosis cells become obvious by TUNEL staining (d), and PCNA expression was downregulated (Po0.001) (e).…”

Section: Discussionmentioning

confidence: 99%

“…19 The extracellular portion of EGFR is Figure 5 Compare to the group of PBS and psiRNA-scr, tumor growth in nude mice in the group of psiRNA-EGFR and panti-EGFR were inhibited (Po0.001) (a), EGFR expression of tumors was downregulated (b), GFAP expression was upregulated (c), apoptosis cells become obvious by TUNEL staining (d), and PCNA expression was downregulated (Po0.001) (e).…”

Section: Discussionmentioning

confidence: 99%

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Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

et al. 2006

Cancer Gene Ther

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Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400-2420) and the 3 0 -coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense-and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense-and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense-and siRNA-treated groups than the control groups. Our results demonstrated that antisense-or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

et al. 2006

Cancer Gene Ther

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“…The gene encodes a protein of 464 amino acids. 49,50 EGFR is composed of an N-terminal extracellular ligand-binding domain, a transmembrane lipophilic segment, and a C-terminal intracellular region containing a tyrosine kinase domain. The EGFR tyrosine kinase modulates cell proliferation and survival through autoactivation of EGFR itself, or through two downstream intermediate pathways: the PIK3CA/AKT1/ MTOR pathway and the RAS/RAF1/MAP2K1/ MAPK1 pathway.…”

Section: Egfr Mutationsmentioning

confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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“…22 The reverse transcription reaction and digoxigenin 11-UTP (Boehringer Mannheim, Indianapolis, IN, USA) labeling were performed with T7 (antisense) and T3 (sense) RNA polymerase, provided in the riboprobe labeling kit following the manufacturer's instruction (Promega, Madison, WI, USA). The labeled probes were digested with deoxyribonuclease, extracted with phenol/chloroform, and precipitated with ethanol.…”

Section: Ishmentioning

confidence: 99%

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas

et al. 2004

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Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n ¼ 8), pituitary adenomas (n ¼ 158), and pituitary carcinomas (n ¼ 7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phosphoepidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.

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Comparative Genomic Sequence Analysis and Isolation of Human and Mouse Alternative EGFR Transcripts Encoding Truncated Receptor Isoforms

Cited by 96 publications

References 50 publications

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

Molecular pathology of lung cancer: key to personalized medicine

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas

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