Increased binding capacity of receptors for the epidermal growth factor in benign thyroid nodules and thyroid malignancies

1993 ◽  
Vol 71 (11) ◽  
Author(s):  
B. Saller ◽  
G. Stapfer ◽  
B. Bein ◽  
R. Hoermann ◽  
F. Spelsberg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Thyroid Nodules ◽  
Binding Capacity ◽  
Epidermal Growth ◽  
Thyroid Malignancies ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Epidermal growth factor in gingival crevicular fluid and its binding capacity in inflamed and non-inflamed human gingiva

1996 ◽  
Vol 41 (7) ◽  
pp. 719-724 ◽  
Author(s):  
Kuang-Min Chang ◽  
Nina Lehrhaupt ◽  
Louis M. Lin ◽  
Jian Feng ◽  
Chi-Ying Wu-Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Gingival Crevicular Fluid ◽  
Binding Capacity ◽  
Human Gingiva ◽  
Epidermal Growth ◽  
Crevicular Fluid

scholarly journals 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts.

1976 ◽  
Vol 71 (1) ◽  
pp. 159-171 ◽  
Author(s):  
G Carpenter ◽  
S Cohen
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Energy Production ◽  
Binding Capacity ◽  
Human Fibroblasts ◽  
Metabolic Energy ◽  
Acid Extraction ◽  
Native Form ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

125I-labeled human epidermal growth factor (hEGF) binds in a specific and saturable manner to human fibroblasts. At 37 degrees C, the cell-bound 125I-hEGF initially may be recovered in a native form by acid extraction; upon subsequent incubation, the cell-bound 125I-hEGF is degraded very rapidly, with the appearance in the medium of 125I-monoiodotyrosine. At 0 degrees C, cell-bound 125I-hEGF is not degraded but slowly dissociates from the cell. The data are consistent with a mechanism in which 125I-hEGF initially is bound to the cell surface and subsequently is internlized before degradation. The degradation is blocked by inhibitors of metabolic energy production (azide, cyanide, dinitrophenol), some protease inhibitors (Tos-Lys-CH2Cl, benzyl guanidobenzoate), a lysosomotropic agent (chloroquine) various local anesthetics (cocaine, lidocaine, procaine), and ammonium chloride. After the binding and degradation of 125I-hEGF the fibroblasts are no longer able to rebind fresh hormone. The binding capacity of these cells is restored by incubation in a serum-containing medium; this restoration is inhibited by cycloheximide or actinomycin D.

Circulating Cytokeratin 19 Fragments in Patients with benign Nodules and Carcinomas of the Thyroid Gland

2008 ◽  
Vol 23 (1) ◽  
pp. 54-57 ◽  
Author(s):  
L. Giovanella ◽  
L. Ceriani ◽  
A. Ghelfo ◽  
M. Maffioli
Keyword(s):  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Differentiated Thyroid Carcinoma ◽  
Cytokeratin 19 ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Benign Nodules ◽  
Thyroid Malignancies ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 (Cyfra 21.1) can be measured by immunometric assays employing specific monoclonal antibodies. The present study was planned to assess the serum expression of Cyfra 21.1 in patients with benign thyroid nodules and thyroid malignancies. We enrolled 135 patients with histologically proven benign thyroid nodules (n=79) and thyroid carcinomas (n=56). No differences were found in serum Cyfra 21.1 levels between patients with benign nodules and patients with carcinomas. When thyroid malignancies were subdivided according to tumor histology, serum Cyfra 21.1 increased significantly from classical differentiated thyroid carcinomas (papillary or follicular) to less differentiated or undifferentiated carcinomas (poorly differentiated or anaplastic). CK19 release into the bloodstream is strongly related to the apoptotic pathway, and particularly to hyperproliferation-related apoptosis. These pathways characterized anaplastic and poorly differentiated thyroid carcinoma but not classical forms of differentiated thyroid carcinoma. Consequently, Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. Additionally, a role of Cyfra 21.1 as a dedifferentiation marker in patients with classical differentiated thyroid carcinomas may be postulated and should be explored by further focused studies.

scholarly journals A rapid decrease in epidermal growth factor-binding capacity accompanies the terminal differentiation of mouse myoblasts in vitro.

1984 ◽  
Vol 98 (2) ◽  
pp. 739-747 ◽  
Author(s):  
R W Lim ◽  
S D Hauschka
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Binding Capacity ◽  
Growth Factor Receptor ◽  
Terminal Differentiation ◽  
Growth Stimulation ◽  
Cycle Arrest ◽  
A Cell ◽  
Epidermal Growth

Specific mitogens stimulate the proliferation and repress the differentiation of mouse myoblasts (MM14). When mitogens are depleted, MM14 cells cease proliferation, commit to terminal differentiation, and become refractory to growth stimulation. The behavior of mitogen receptors during the transition from a proliferative to a permanently postmitotic state was examined using the epidermal growth factor receptor (EGFR) as a model system. Whereas proliferating myoblasts bound substantial amounts of EGF, their binding capacity declined rapidly upon exposure to low-mitogen medium. The decline became irreversible when a cell differentiated. Within 24 h, less than 5% of the original EGF binding capacity remained. Since the ability to internalize and degrade bound EGF was unaffected, the change presumably reflected a decrease in EGFR availability. Several observations indicated that loss of EGFR following mitogen removal is related to differentiation rather than the result of starvation or cell-cycle arrest. First, the decline is correlated with the absence of a single mitogen (fibroblast growth factor) and is independent of serum concentrations. Second, myoblasts that are either cycling through G1 or arrested at G0, but prevented from differentiating, all bind large amounts of EGF. These findings suggest that specific reduction in mitogen receptors could be part of a mechanism whereby terminally differentiating cells become refractory to mitogenic stimulation.

High-Performance Liquid Chromatography of 125I-Labeled Mouse Epidermal Growth Factor Radioiodinated by Six Different Methods

1992 ◽  
Vol 38 (5) ◽  
pp. 681-686 ◽  
Author(s):  
C B Kienhuis ◽  
J J Heuvel ◽  
H A Ross ◽  
J A Foekens ◽  
T J Benraad
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
High Performance ◽  
Binding Capacity ◽  
Reversed Phase ◽  
Iodine Monochloride ◽  
Reversed Phase Hplc ◽  
Hplc Column ◽  
Epidermal Growth ◽  
Chloramine T

Abstract Six different procedures for radioiodination of mouse epidermal growth factor (EGF) all resulted in a heterogeneous 125I-labeled EGF preparation, as analyzed by reversed-phase HPLC. EGF preparations that had been iodinated with Chloramine T, lodogen, or lodo-beads were found mainly to consist of oxidized 125I-labeled EGF moieties. In contrast, the heterogeneous 125I-labeled EGF preparations obtained by using iodine monochloride, Protag-125, or lactoperoxidase-glucose oxidase-coupled beads (Enzymobeads) contained insignificant amounts of oxidized EGF entities. Ligand equivalence analysis (LEA) of distinct HPLC column fractions, obtained after preparative separation of Chloramine T-125I-labeled EGF, showed that the receptor-binding affinity of the tracer in all subfractions was less than the affinity of unlabeled EGF. This implies that HPLC purification of these 125I-labeled EGF preparations does not yield 125I-labeled EGF preparations with ligand equivalence. However, all but one HPLC column fraction of Enzymobeads-125I-labeled EGF showed ligand equivalence. Despite the small amount of the nonequivalent component in the Enzymobeads-labeled tracer, the nonchromatographed 125I-labeled EGF preparation showed ligand equivalence. No significant differences were observed in the maximal binding capacity of the different 125I-labeled EGF preparations.

scholarly journals Spatial Localization of m-Calpain to the Plasma Membrane by Phosphoinositide Biphosphate Binding during Epidermal Growth Factor Receptor-Mediated Activation

2006 ◽  
Vol 26 (14) ◽  
pp. 5481-5496 ◽  
Author(s):  
Hanshuang Shao ◽  
Jeff Chou ◽  
Catherine J. Baty ◽  
Nancy A. Burke ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase C ◽  
Cell Body ◽  
Wound Repair ◽  
Egf Receptor ◽  
Binding Capacity ◽  
Dependent Manner ◽  
Epidermal Growth

ABSTRACT Calpain activity is required for de-adhesion of the cell body and rear to enable productive locomotion of adherent cells during wound repair and tumor invasion. Growth factors activate m-calpain (calpain 2, CAPN2) via ERK/mitogen-activated protein kinases, but only when these kinases are localized to the plasma membrane. We thus hypothesized that m-calpain is activated by epidermal growth factor (EGF) only when it is juxtaposed to the plasma membrane secondary to specific docking. Osmotic disruption of NR6 fibroblasts expressing the EGF receptor demonstrated m-calpain being complexed with the substratum-adherent membrane with this increasing in an EGF-dependent manner. m-Calpain colocalized with phosphoinositide biphosphate (PIP2) with exogenous phospholipase C removal of phosphoinositides, specifically, PI(4,5)P2 but not PI(4)P1 or PIP3, releasing the bound m-calpain. Downregulation of phosphoinositide production by 1-butanol resulted in diminished PIP2 in the plasma membrane and eliminated EGF-induced calpain activation. This PIP2-binding capacity resided in domain III of calpain, which presents a putative C2-like domain. This active conformation of this domain appears to be partially masked in the holoenzyme as both activation of m-calpain by phosphorylation at serine 50 and expression of constitutively active phosphorylation mimic glutamic acid-increased m-calpain binding to the membrane, consistent with blockade of this cascade diminishing membrane association. Importantly, we found that m-calpain was enriched toward the rear of locomoting cells, which was more pronounced in the plasma membrane footprints; EGF further enhanced this enrichment, in line with earlier reports of loss of PIP2 in lamellipodia of motile cells. These data support a model of m-calpain binding to PIP2 concurrent with and likely to enable ERK activation and provides a mechanism by which cell de-adhesion is directed to the cell body and tail as phospholipase C-γ hydrolyzes PIP2 in the protruding lamellipodia.

Characterization and localization of receptors for epidermal growth factor in ovine skin

1989 ◽  
Vol 121 (1) ◽  
pp. 81-NP ◽  
Author(s):  
P. C. Wynn ◽  
I. G. Maddocks ◽  
G. P. M. Moore ◽  
B. A. Panaretto ◽  
P. Djura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Recombinant Dna ◽  
Morphological Changes ◽  
Binding Capacity ◽  
Egf Receptors ◽  
Outer Root Sheath ◽  
Epidermal Growth

ABSTRACT Specific receptor sites for murine epidermal growth factor (EGF) have been characterized and their distribution determined in ovine skin. Binding of 125I-labelled EGF to skin membrane particles was temperature- and time-dependent, with equilibrium being reached within 1 h at 23 °C. Analysis of skin biopsies collected from ten castrated Merino sheep demonstrated the presence of a single class of saturable, high-affinity binding sites with a dissociation constant of 64 ± 4 (s.e.m.) pmol/l and a binding capacity of 33·8 ± 4·5 fmol/mg protein. Skin particle binding of 125I-labelled EGF was inhibited equipotently by mouse salivary gland EGF, EGF produced by recombinant DNA procedures and urogastrone. The EGF peptides 1–48, 6–53 and 7–53, derived from the native molecule by enzymatic cleavage, were much less potent. The relative binding potency of these molecules was correlated with their ability to induce precocious eyelid opening in mice and to inhibit wool follicle activity. Synthetic fragments representing the major structural domains of the EGF molecule (EGF(29–44), EGF(33–42) and EGF(3–31)) were inactive in both the receptor and bioassays. Auto-radiography of skin sections incubated with 125I-labelled EGF in vitro or of sections from skin which was perfused with 125I-labelled EGF in vivo demonstrated that EGF receptors were localized in undifferentiated cells of the epidermis and sebaceous glands, the inner and outer root sheath and bulb of wool follicles and in dermal arterioles. Differences in receptor concentration were observed between follicles following in-vivo perfusion of 125I-labelled EGF but not when the in-vitro labelling technique was used. The presence of receptors in these regions is consistent with the morphological changes in sheep skin in reponse to EGF administration which have been reported previously. Journal of Endocrinology (1989) 121, 81–90

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