Heterogeneity in Epidermal Growth Factor Responsiveness and Tumor Growth of Human Maxillary Cancer Cell Lines

1992 ◽  
Vol 101 (6) ◽  
pp. 519-524 ◽  
Author(s):  
Sohtaro Komiyama ◽  
Shohji Kudoh ◽  
Katsuko Matsui ◽  
Hiromoto Mizoguchi ◽  
Hiroshi Miyazaki ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tumor Growth ◽  
Cell Lines ◽  
Nude Mice ◽  
Egf Receptor ◽  
Slow Growth ◽  
Maxillary Cancer ◽  
Epidermal Growth ◽  
Intermediate Rate

We have established three cell lines (IMC-2, IMC-3, and IMC-4) from a human maxillary tumor, which exhibited different sensitivities to epidermal growth factor (ECF). It was inhibitory to colony-forming abilities of IMC-3 and IMC-4 cells in culture, while it affected that of IMC-2 cells slightly if at all. The differential sensitivities to EGF among the three cell lines were reproducibly observed when several cell sublines were further established from tumors appearing in nude mice. Saturation-binding kinetics with 125I-EGF showed similar levels of EGF-binding activities among the three cell lines. However, IMC-2, IMC-3, and IMC-4 showed almost similar sensitivities to cisplatin. Autophosphorylation of EGF receptor in the presence of EGF proceeded at similar levels among the three cell lines. Tumor growth was followed in nude mice when IMC-2, IMC-3, and IMC-4 at 1 × 107 cells were inoculated. The IMC-2 tumors enlarged at much faster rates than the other two cell lines. The IMC-4 tumors showed very slow growth rates, and IMC-3 tumors enlarged at an intermediate rate. These data suggest that the maxillary tumor used comprised cell populations that differed in their growth behaviors in response to EGF.

scholarly journals Expression and biosynthetic variation of the epidermal growth factor receptor in human hepatocellular carcinoma-derived cell lines.

1988 ◽  
Vol 8 (1) ◽  
pp. 25-34 ◽  
Author(s):  
C R Carlin ◽  
D Simon ◽  
J Mattison ◽  
B B Knowles
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Amplification ◽  
Egf Receptor ◽  
Hepatoma Cell ◽  
Receptor Gene ◽  
Epidermal Growth

Expression of the epidermal growth factor (EGF) was analyzed in six human hepatocellular carcinoma-derived and one human hepatoblastoma-derived cell line, each of which retained the differentiated phenotype and functions of the parenchymal hepatocyte. The level of receptor expression of each hepatoma cell line was similar to that of the normal human fibroblast, approximately 10(5) molecules per cell. However, NPLC/PRF/5, a subline of the PLC/PRF/5 cell line obtained following reestablishment of a xenograft tumor in vitro, was found to express 4 x 10(6) high-affinity EGF receptor molecules per cell. Proliferation of the NPLC/PRF/5 cell line was inhibited in the presence of nanomolar quantities of ligand. Receptor overexpression was found to result from EGF receptor gene amplification without apparent rearrangement of the EGF receptor coding sequences. Although cell-specific variability in posttranslational processing of EGF receptor N-linked oligosaccharides in the hepatoma cell lines was found, no difference between the receptors in PLC/PRF/5 and NPLC/PRF/5 was observed and no aberrant receptor-related species were detected. EGF receptor gene amplification in the NPLC/PRF/5 cell line is probably a reflection of genome instability and selection of variants with augmented growth potential in limiting concentrations of EGF in vivo. When viewed in this light, EGF receptor overexpression could represent a manifestation of tumor progression in the EGF-responsive hepatocyte.

Expression and biosynthetic variation of the epidermal growth factor receptor in human hepatocellular carcinoma-derived cell lines

1988 ◽  
Vol 8 (1) ◽  
pp. 25-34
Author(s):  
C R Carlin ◽  
D Simon ◽  
J Mattison ◽  
B B Knowles
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Amplification ◽  
Egf Receptor ◽  
Hepatoma Cell ◽  
Receptor Gene ◽  
Epidermal Growth

Expression of the epidermal growth factor (EGF) was analyzed in six human hepatocellular carcinoma-derived and one human hepatoblastoma-derived cell line, each of which retained the differentiated phenotype and functions of the parenchymal hepatocyte. The level of receptor expression of each hepatoma cell line was similar to that of the normal human fibroblast, approximately 10(5) molecules per cell. However, NPLC/PRF/5, a subline of the PLC/PRF/5 cell line obtained following reestablishment of a xenograft tumor in vitro, was found to express 4 x 10(6) high-affinity EGF receptor molecules per cell. Proliferation of the NPLC/PRF/5 cell line was inhibited in the presence of nanomolar quantities of ligand. Receptor overexpression was found to result from EGF receptor gene amplification without apparent rearrangement of the EGF receptor coding sequences. Although cell-specific variability in posttranslational processing of EGF receptor N-linked oligosaccharides in the hepatoma cell lines was found, no difference between the receptors in PLC/PRF/5 and NPLC/PRF/5 was observed and no aberrant receptor-related species were detected. EGF receptor gene amplification in the NPLC/PRF/5 cell line is probably a reflection of genome instability and selection of variants with augmented growth potential in limiting concentrations of EGF in vivo. When viewed in this light, EGF receptor overexpression could represent a manifestation of tumor progression in the EGF-responsive hepatocyte.

scholarly journals Epidermal growth factor-induced proliferation of collecting duct cells from Oak Ridge polycystic kidney mice involves activation of Na+/H+ exchanger

2014 ◽  
Vol 307 (6) ◽  
pp. C554-C560 ◽  
Author(s):  
Sonya D. Coaxum ◽  
Mary G. Blanton ◽  
Alisha Joyner ◽  
Tanjina Akter ◽  
P. Darwin Bell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Cell Lines ◽  
Egf Receptor ◽  
Collecting Duct ◽  
Polycystic Kidney ◽  
Oak Ridge ◽  
Erk Phosphorylation ◽  
Epidermal Growth

Epidermal growth factor (EGF) is linked to the pathogenesis of polycystic kidney disease (PKD). We explored signaling pathways activated by EGF in orpk cilia (−) collecting duct cell line derived from a mouse model of PKD (hypomorph of the Tg737/ Ift88 gene) with severely stunted cilia, and in a control orpk cilia (+) cell line with normal cilia. RT-PCR demonstrated mRNAs for EGF receptor subunits ErbB1, ErbB2, ErbB3, ErbB4, and mRNAs for Na+/H+ exchangers (NHE), NHE-1, NHE-2, NHE-3, NHE-4, and NHE-5 in both cell lines. EGF stimulated proton efflux in both cell lines. This effect was significantly attenuated by MIA, 5-( n-methyl- N-isobutyl) amiloride, a selective inhibitor of NHE-1 and NHE-2, and orpk cilia (−) cells were more sensitive to MIA than control cells ( P < 0.01). EGF significantly induced extracellular signal-regulated kinase (ERK) phosphorylation in both cilia (+) and cilia (−) cells (63.3 and 123.6%, respectively), but the effect was more pronounced in orpk cilia (−) cells ( P < 0.01). MIA significantly attenuated EGF-induced ERK phosphorylation only in orpk cilia (−) cells ( P < 0.01). EGF increased proliferation of orpk cilia (+) cells and orpk cilia (−) cells, respectively, and MIA at 1–5 μM attenuated EGF-induced proliferation in orpk cilia (−) cells without affecting proliferation of orpk cilia (+) cells. EGF-induced proliferation of both cell lines was significantly decreased by the EGFR tyrosine kinase inhibitor AG1478 and MEK inhibitor PD98059. These results suggest that EGF exerts mitogenic effects in the orpk cilia (−) cells via activation of growth-associated amiloride-sensitive NHEs and ERK.

scholarly journals Cross talk between epidermal growth factor (EGF) receptor and extra nuclear steroid receptors in cell lines

2010 ◽  
Vol 327 (1-2) ◽  
pp. 19-24 ◽  
Author(s):  
Antimo Migliaccio ◽  
Gabriella Castoria ◽  
Pia Giovannelli ◽  
Ferdinando Auricchio
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Lines ◽  
Cross Talk ◽  
Egf Receptor ◽  
Steroid Receptors ◽  
Epidermal Growth

scholarly journals Two independent mechanisms for escaping epidermal growth factor-mediated growth inhibition in epidermal growth factor receptor-hyperproducing human tumor cells.

1988 ◽  
Vol 107 (2) ◽  
pp. 791-799 ◽  
Author(s):  
M Hirai ◽  
S Gamou ◽  
S Minoshima ◽  
N Shimizu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Inhibition ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Blot Analysis ◽  
Egf Receptor ◽  
Egfr Gene ◽  
Epidermal Growth

Human squamous cell carcinoma cell lines often possess increased levels of epidermal growth factor (EGF) receptor. The growth of these EGF receptor-hyperproducing cells is usually inhibited by EGF. To investigate the mechanism of EGF-mediated inhibition of cell growth, variants displaying alternate responses to EGF were isolated from two squamous cell carcinoma lines, NA and Ca9-22; these cell lines possess high numbers of the EGF receptor and an amplified EGF receptor (EGFR) gene. The variants were isolated from NA cells after several cycles of EGF treatment and they have acquired EGF-dependent growth. Scatchard plot analysis revealed a decreased level of EGF receptor in these ER variants as compared with parental NA cells. Southern blot analysis and RNA dot blot analysis demonstrated that the ER variants had lost the amplified EGFR gene. One variant isolated from Ca9-22 cells, CER-1, grew without being affected by EGF. CER-1 cells had higher numbers of EGF receptor than parental Ca9-22 but similar EGFR gene copy number. Flow cytometric analysis indicated an increase in ploidy and cell volume which may give rise to the increase in receptor number per cell. The EGF receptors on both Ca9-22 and CER-1 cells were autophosphorylated upon EGF exposure in a similar manner suggesting no obvious alteration in receptor tyrosine kinase. However, very efficient down-regulation of the EGF receptor occurred in CER-1 cells. These data suggest two independent mechanisms by which EGF receptor-hyperproducing cells escape EGF-mediated growth inhibition: one mechanism is common and involves the loss of the amplified EGFR genes, and another is novel and involves the efficient down-regulation of the cell-surface receptor.

Epidermal growth factor stimulates cell proliferation and inhibits iodide uptake of FRTL-5 cells in vitro

1995 ◽  
Vol 145 (3) ◽  
pp. 513-520 ◽  
Author(s):  
L M Asmis ◽  
H Gerber ◽  
J Kaempf ◽  
H Studer
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Lines ◽  
Egf Receptor ◽  
Cell Function ◽  
Iodide Uptake ◽  
Monolayer Cultures ◽  
Epidermal Growth

Abstract In accordance with the available data most authors conclude that epidermal growth factor (EGF) has very little or no effect on FRTL-5 cells. This has been viewed as a serious handicap of this cell line. In the present study we cultivated three strains of FRTL-5 cells from different sources and assessed their response to EGF with regard to proliferation, function and differentiation. Cell proliferation was assessed by counting in a Coulter cell counter after culturing cells at suboptimal conditions in well plates. Cell function was studied by measuring iodide uptake. Cell differentiation was examined immunocytochemically by staining monolayer cultures for thyroglobulin (Tg) and EGF receptor (EGFr) as well as morphologically by microscopical evaluation of monolayer cultures. All three FRTL-5 cell lines investigated express EGFr. In two wild type FRTL-5 cell lines EGF stimulates growth, an effect that is enhanced by the presence of TSH, and partially inhibits iodide uptake. A third mutated strain of FRTL-5 cells does not respond to EGF. Tg expression can be demonstrated immunocytochemically in EGF-treated cells as well as in controls. Morphologically, in monolayer culture EGF-treated cells cannot be distinguished from controls. Contrary to previous reports, these studies demonstrate EGF effects on FRTL-5 cells that are consistent with EGF effects established in other thyroid follicular cells. Journal of Endocrinology (1995) 145, 513–520

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