Abstract:
:Recently, we isolated 4 distinct kinds of single chain antibody against human EGF receptor (EGFR) after screening the Keio phage display scFv library by using two methods of target-guided proximity labeling. In the current study, these monovalent scFv antibodies were converted to bivalent IgGs of humanized forms (hIgGs) by recombinant technology using the specially designed expression vectors followed by protein production in CHO cells. The resulting recombinant hIgGs were examined for their binding specificity using several different transformed human BJ cell lines that express deletion mutants of EGFR, each lacking one of 4 distinct extracellular domains (L1, L2, C1 and C2). Immuno-fluorescent microscopy and immuno-precipitation assay on these cells indicated that 4 distinct kinds of hIgGs bind to one of 3 different domains (L1, C1 and C2). Then, these hIgGs were further examined for biological effects on human A431 cancer cells, which overexpress EGFR. The results indicated that hIgG38 binding to L1 and hIgG45 binding to C2 substantially suppressed the EGF-induced phosphorylation of EGFR, resulting in the growth inhibition of A431 cancer cells. On the contrary, hIgG40 binding to C1 and hIgG42 binding to another site (epitope) of C2 exhibited no such inhibitory effects. Thus, the newly produced four recombinant hIgG antibodies recognize 4 different sites (epitopes) in 3 different extracellular domains of EGFR and exhibit different biological effects on cancer cells. These characteristics are somewhat different from the currently utilized therapeutic anti-EGFR antibodies. Hence, these hIgG antibodies will be invaluable as a research tool for the detailed molecular analysis of the EGFR-mediated signal transduction mechanism and more importantly a possible application as new therapeutic agents to treat certain types of cancers.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Chang C,Takayanagi A,Yoshida T,Shimizu Ndoi
10.1016/j.yexcr.2013.03.002subject
Has Abstractpub_date
2013-05-01 00:00:00pages
1146-55issue
8eissn
0014-4827issn
1090-2422pii
S0014-4827(13)00110-9journal_volume
319pub_type
杂志文章abstract::In a previous study we have shown that triiodothyronine (T3) added to a serum-free medium supplemented with insulin, transferrin, and selenous acid (ITS) can stimulate Caco-2 cell differentiation. In this study we have focused on the effects of T3 on sucrase activity. The results obtained demonstrate that T3 (50 nM) d...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1996.0041
更新日期:1996-02-01 00:00:00
abstract::We have investigated the gene targeting frequency at the hprt locus in a range of embryonic stem cell lines selected for variations in cell cycle parameters. Our results show that targeting frequency varies with cell line by as much as 12-fold between nonisogenic lines and 3-fold between isogenic lines and that a noni...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1996.3470
更新日期:1997-03-15 00:00:00
abstract::The Saccharomyces cerevisiae ALG7 gene, which functions by initiating the dolichol pathway of protein N-glycosylation, displays properties of an early growth-response gene. To initiate studies of the involvement of ALG7 in cellular proliferation, we have now more precisely analyzed ALG7 expression in the G1 phase of c...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1995.1255
更新日期:1995-08-01 00:00:00
abstract::Over-activation of beta-catenin/TCF signaling has been frequently observed in hepatocellular carcinoma (HCC). Better understanding the molecular mechanism for the aberrant activation of beta-catenin/TCF signaling would provide novel insights into the treatment of this malignancy. In this study, we have shown that the ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2017.06.014
更新日期:2017-09-15 00:00:00
abstract::Uterine fibroids, also known as uterine leiomyomas, are a benign tumor of the human uterus and the commonest estrogen-dependent benign tumor found in women. Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. The role of myocardin and its relationship with ERα in uterine fibro...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2016.11.007
更新日期:2017-01-01 00:00:00
abstract::Epidermal growth factor (EGF) has been shown to be a potent mitogen for epidermal cells both in vitro and in vivo, thus contributing to the development of an organism. It has recently become clear that peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) expression and activation is involved in the c...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2008.06.013
更新日期:2008-10-15 00:00:00
abstract::We report here the identification and characterization of STIP, a multi-domain nuclear protein that contains a G-patch, a coiled-coil, and several short tryptophan-tryptophan repeats highly conserved in metazoan species. To analyze their functional role in vivo, we cloned nematode stip-1 genes and determined the spati...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2007.01.003
更新日期:2007-04-15 00:00:00
abstract::Like most epithelial cells that are isolated from tissues and placed in culture, the phenotype of human retinal pigment epithelial cells (RPE) in vitro is more variable than for the same cells in situ. The phenotypic heterogeneity of the cultures has been attributed to varying stages of differentiation of the cells in...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1994.1176
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND:Metastatic and/or recurrent breast carcinomas are leading causes of cancer-related death worldwide. Breast cancer stem cells (BCSCs) have been implicated in cancer metastases and progression, thus, the need for the discovery and development of effective BCSCs-specific therapies against metastatic and triple ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2018.07.008
更新日期:2018-09-15 00:00:00
abstract::Signalling from the extracellular matrix (ECM) is a fundamental cellular input that sustains proliferation, opposes cell death and regulates differentiation. Through integrins, cells perceive both the chemical composition and physical properties of the ECM. In particular, cell behaviour is profoundly influenced by the...
journal_title:Experimental cell research
pub_type: 杂志文章,评审
doi:10.1016/j.yexcr.2015.10.034
更新日期:2016-04-10 00:00:00
abstract::Developmental studies have demonstrated that the vascular smooth muscle cells (VSMC) present within the elastic arteries are differentiated from two definitive origins, the neural crest and the mesoderm. Cells from these distinct progenitors differ in their ability to determine long-range spatial order of the extracel...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1996.0258
更新日期:1996-08-25 00:00:00
abstract::Accumulating evidence indicates that elevated S100P promotes the pathogenesis of cancers, including colon cancer. S100P exerts its effects by binding to and activating the Receptor for Advance Glycation End-products (RAGE). The effects of up-regulated S100P/RAGE signaling on cell functions are well documented. Despite...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2013.05.009
更新日期:2013-08-01 00:00:00
abstract::SIRT5 has a wide range of functions in different cellular processes such as glycolysis, TCA cycle and antioxidant defense, which mediates lysine desuccinylation, deglutarylation and demalonylation. Recent evidences have implicated that SIRT5 is a potential suppressor of gastric cancer (GC). However, the underlying mec...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2019.06.028
更新日期:2019-09-15 00:00:00
abstract::Template-activating factors I (TAF-I) alpha and beta have been identified as chromatin remodeling factors from human HeLa cells. TAF-I beta corresponds to the protein encoded by the set gene, which was found in an acute undifferentiated leukemia as a fusion version with the can gene via chromosomal translocation. To d...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1997.3930
更新日期:1998-05-01 00:00:00
abstract::The biosynthesis of type XI and type II collagens was examined using a stable rat chondrocyte cell line established by W. E. Horton et al. (1988, Exp. Cell Res. 178, 457-468.). These cells (IRC; immortalized rat chondrocytes) were created by transformation with a murine retrovirus carrying the v-myc and v-raf oncogene...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1994.1169
更新日期:1994-07-01 00:00:00
abstract::The bone-related transcription factor Runx2 (Cbfa1) has been extensively shown to regulate osteoblast differentiation and function. Recent studies demonstrate that Runx2 is also a positive regulator of chondrocyte maturation and vascular invasion in cartilage. Runx2 activity can be modulated in several ways, including...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2004.05.025
更新日期:2004-09-10 00:00:00
abstract::MicroRNAs (miRNAs) are a class of small non-coding RNAs that repress the expression of their target genes post-transcriptionally. MiRNAs participate in the regulation of a variety of biological processes, including development and diseases. However, the functional role and molecular mechanism by which miRNAs regulate ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2012.06.018
更新日期:2012-11-01 00:00:00
abstract::The adaptor protein Shb has previously been shown to regulate apoptosis in response to cytokines and inhibitors of angiogenesis although the mechanisms governing these effects have remained obscure. We currently demonstrate interactions between Shb and c-Abl and that Shb regulates c-Abl kinase activity. The data sugge...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2006.10.011
更新日期:2007-01-15 00:00:00
abstract:BACKGROUND AND OBJECTIVE:In recent years, immunotherapy for the treatment of tumors have been established. Dendritic cells (DCs) are extremely efficient and professional antigen presenting cells (APCs), which are an important target for immune therapeutic interventions in cancer. In present study, we investigated wheth...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2016.10.019
更新日期:2016-12-10 00:00:00
abstract::The phosphorylation state of the CD18-chain of beta 2-integrins have been shown not to mediate changes in the avidity of these receptors (i.e., inside-out signaling); however, no alternative functional significance has been proposed. Our study focused on how changes in the phosphorylation state of beta 2-integrin-rece...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1995.1073
更新日期:1995-03-01 00:00:00
abstract::Products of the Neuregulin-1 (Nrg-1) gene, along with the ErbB family of receptor tyrosine kinases through which Nrg-1 ligands signal, play a critical role during cardiovascular development. Through studies of genetically manipulated mice, as well as studies in cells isolated from adult hearts, it appears that Nrg-1/E...
journal_title:Experimental cell research
pub_type: 杂志文章,评审
doi:10.1016/j.yexcr.2008.08.015
更新日期:2009-02-15 00:00:00
abstract::Our previous studies have showed that tumor-derived autophagosomes (termed "DRibbles") induce B cell activation, resulting in antibody production and cytokine secretion. Unexpectedly, we found that unfractionated splenocytes produced a higher level of antibody and cytokine than that of purified B cells. In the current...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2014.10.015
更新日期:2015-02-15 00:00:00
abstract::Metastatic progression is a major cause of mortality in cervical cancers, but factors regulating migratory and pre-metastatic cell populations remain poorly understood. Here, we sought to assess whether a SUV39H1-low chromatin state promotes migratory cell populations in cervical cancers, using meta-analysis of data f...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2019.02.010
更新日期:2019-05-15 00:00:00
abstract::Breast cancer is a common malignancy and a major cause of death in women worldwide. The immunomodulatory role of B cells is being increasingly recognized in autoimmune diseases and cancers. In recent years, immunotherapeutic strategies that upregulate the patient's own antitumor T cell responses have shown promise in ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2017.10.013
更新日期:2017-12-01 00:00:00
abstract::DNA methylation in F9 embryonal carcinoma cells at various stages of retinoic acid-induced differentiation was compared to that in immortalized differentiated derivatives of this cell line. Different repetitive sequences, such as L1 LINE, GAPDH pseudogenes, and major and minor satellite DNA, lost their methylation to ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1994.1029
更新日期:1994-02-01 00:00:00
abstract::Tetrahymena 14-nm filament-forming protein (49K protein) is a structural protein which is involved in activity of the pronuclei during conjugation (O. Numata, T. Sugai, and Y. Watanabe (1985) Nature (London) 314, 192-194). Using monoclonal and polyclonal antibodies, we here demonstrate the presence of a cross-reactive...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(91)90554-8
更新日期:1991-03-01 00:00:00
abstract::Earlier we reported the undetectable level of endothelin (ET)-1 mRNA in aorta from young donors, in contrast to the detectable levels in older donors (Lab. Invest. 67, 210-217, 1992). We also found that the synthesis of ET-1 peptide is elevated in cultured endothelial cells from the aorta of over-50-year-old donors. I...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1994.1051
更新日期:1994-03-01 00:00:00
abstract::ING1b is the most studied ING family protein and perhaps the most ubiquitously and abundantly expressed. This protein is involved in the regulation of various biological functions ranging from senescence, cell cycle arrest, apoptosis, to DNA repair. ING1b is upregulated by UV irradiation and enhances the removal of bu...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2007.02.010
更新日期:2007-05-01 00:00:00
abstract::Celiac disease (CD) is a multisystemic autoimmune inflammation of the intestinal tract induced by wheat gluten and related cereals in HLA-DQ2/8 positive individuals. An essential role in the pathogenesis of CD is played by a fraction of the peptic-tryptic digest of gluten, Frazer's Fraction (FF). Here, we investigate ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2009.06.026
更新日期:2009-11-15 00:00:00
abstract::The tyrosine phosphatase PTP1B is an important regulator of cell function. In living cells PTP1B activity is restricted to the vicinity of the endoplasmic reticulum (ER) by post-translational C-terminal attachment of PTP1B to the ER membrane network. In our study we investigated the membrane anchor of PTP1B by use of ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2007.05.025
更新日期:2007-09-10 00:00:00