A polyamine pathway-mediated mitogenic mechanism in enterochromaffin-like cells of Mastomys

1998 ◽  
Vol 275 (2) ◽  
pp. G370-G376 ◽  
Author(s):  
M. Kidd ◽  
L. H. Tang ◽  
S. W. Schmid ◽  
K. Miu ◽  
I. M. Modlin
Keyword(s):  
Dna Synthesis ◽  
Proliferative Response ◽  
Transforming Growth Factor ◽  
Cell Transformation ◽  
Polyamine Biosynthesis ◽  
Transforming Growth Factor Α ◽  
Ecl Cells ◽  
Ecl Cell ◽  
Factor Α ◽  
Rate Limiting

We have previously demonstrated that in Mastomys species proliferation of gastric enterochromaffin-like (ECL) cells is predominantly regulated by gastrin and by transforming growth factor-α (TGF-α) in the naive and neoplastic state, respectively. In this study we examined whether these intracellular mitogenic responses are mediated by polyamines and ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine biosynthesis. An ECL cell preparation of high purity was used to measure the effect of the polyamine derivatives putrescine, spermidine, and spermine on DNA synthesis by bromodeoxyuridine uptake. Both putrescine and spermidine augmented gastrin-stimulated, but not basal, DNA synthesis in naive cells. This proliferative response correlated with an increase in ODC activity that was partially inhibited (20%) by difluoromethylornithine (DFMO), an inhibitor of ODC (IC50, 30 pM). In contrast, all polyamines increased both basal and TGF-α-stimulated DNA synthesis as well as ODC activity in tumor ECL cells. DFMO completely inhibited the proliferative response of TGF-α (IC50, 3 pM). Thus polyamine biosynthesis is involved in proliferation of ECL cells and in particular the mitogenesis of tumor cells, suggesting a role for this pathway in the regulation of ECL cell transformation.

Transforming growth factor-α directly augments histidine decarboxylase and vesicular monoamine transporter 2 production in rat enterochromaffin-like cells

2004 ◽  
Vol 286 (3) ◽  
pp. G508-G514 ◽  
Author(s):  
Hideaki Kazumori ◽  
Shunji Ishihara ◽  
Mohammad A. K. Rumi ◽  
Cesar F. Ortega-Cava ◽  
Yasunori Kadowaki ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Histidine Decarboxylase ◽  
Vesicular Monoamine Transporter ◽  
Vesicular Monoamine Transporter 2 ◽  
Transforming Growth Factor Α ◽  
Ecl Cells ◽  
Factor Α

For the production and vesicle storage of histamine, Enterochromaffin-like (ECL) cells express histidine decarboxylase (HDC) and vesicular monoamine transporter 2 (VMAT2). Although HDC and VMAT2 show dynamic changes during gastric ulcer healing, the control system of their expression has not been fully investigated. In the present study, we investigated the effect of transforming growth factor-α (TGF-α) and proinflammatory cytokines on HDC and VMAT2 expression in rat ECL cells. Time course changes in the expression of TGF-α during the healing of acetic acid-induced ulcers were studied. EGF receptor (EGFR) expression was also examined in ECL cells, whereas the direct effects of TGF-α and proinflammatory cytokines on HDC and VMAT2 expression in ECL cells were investigated using in vivo and in vitro models. During the process of ulcer healing, expression of TGF-α mRNA was markedly augmented. Furthermore, EGFR was identified in isolated ECL cells. TGF-α stimulated HDC and VMAT2 mRNA expression and protein production and also increased histamine release from ECL cells. Selective EGFR tyrosine kinase inhibitor tyrphostin AG1478 almost completely inhibited HDC and VMAT2 gene expression induced by TGF-α in vivo and in vitro. During gastric mucosal injury, TGF-α was found to stimulate ECL cell functions by increasing HDC and VMAT2 expression.

Transforming growth factor-α: receptor binding and action on DNA synthesis in the sheep mammary gland

1995 ◽  
Vol 144 (1) ◽  
pp. 165-171 ◽  
Author(s):  
C D Moorby ◽  
J A Taylor ◽  
I A Forsyth
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Binding Sites ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Mammary Development ◽  
Transforming Growth Factor Α ◽  
Pregnant Sheep ◽  
Igf I ◽  
Factor Α

Abstract Microsome fractions prepared from the mammary glands of non-pregnant, pregnant and lactating sheep have been used to study binding of 125I-labelled transforming growth factor-α (TGF-α). Binding was dependent on microsomal protein concentration, time and temperature. It showed the characteristics of an epidermal growth factor (EGF) receptor, being displaced by TGF-α and EGF, but not by insulin or IGF-I. The non-linear curve fitting program LIGAND was used to determine affinity and number of binding sites. A single class of high-affinity binding sites was found. The apparent dissociation constant (Kd) was similar in all physiological states (2·43±0·27 mol/l × 10−10, n=23). Numbers of binding sites were lower in late-pregnant (20 weeks) and lactating sheep (14·07± 2·45 fmol/mg protein, n=10) than in non-pregnant, 10-or 15-week pregnant sheep (43·04±5·93 fmol/mg protein, n=13). DNA synthesis by mammary alveolar epithelial cells cultured on collagen gels was increased twofold by TGF-a (maximum response at 10 μg/l; 1·8 nmol/l) but not by EGF. Cells derived from 15- to 20-week pregnant sheep responded significantly to TGF-α on day 3 of culture, but the response was delayed to day 4–5 of culture in cells from other physiological states. Dose–response was not significantly affected. TGF-α and IGF-I produced an additive effect on DNA synthesis. Oestradiol (10−12 to 10−9 m), a potential stimulator of the TGF-α gene, did not stimulate DNA synthesis alone, or in combination with IGF-I. It is concluded that growth factors acting via the EGF receptor play a role in ruminant mammary development, but whether they mediate oestradiol effects remains unresolved. Journal of Endocrinology (1995) 144, 165–171

Effects of transforming growth factor-α on chicken adipocyte precursor cells in vitro

1992 ◽  
Vol 134 (2) ◽  
pp. 163-168 ◽  
Author(s):  
S. C. Butterwith ◽  
C. D. Peddie ◽  
C. Goddard
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Transforming Growth Factor Α ◽  
Igf I ◽  
Factor Α ◽  
Adipocyte Precursor

ABSTRACT The hyperplastic capacity of adipose tissue resides in a group of fibroblast-like adipocyte precursor cells. There is evidence to suggest that their proliferation and differentiation is regulated by insulin-like growth factor-I (IGF-I) and transforming growth factor-β (TGF-β) but there is less information about other growth factors which may also participate in adipocyte precursor cell hyperplasia. Transforming growth factor-α (TGF-α) is a 50 amino acid polypeptide which has been shown to stimulate proliferation in both neoplastic and normal cell types acting through the epidermal growth factor (EGF) receptor. We have studied the regulation of DNA synthesis and the activity of lipoprotein lipase by TGF-α in chicken adipocyte precursor cells in vitro. Both TGF-α and EGF stimulated incorporation of [3H]thymidine into DNA in a dose-dependent manner. TGF-α was approximately 180-fold more potent than EGF. Addition of TGF-α in combination with IGF-I, TGF-β1 or platelet-derived growth factor produced a synergistic increase in DNA synthesis. Short-term incubation with TGF-α reduced lipoprotein lipase activity by 23%. These results show that TGF-α is a potent mitogen in these adipocyte precursor cells and can inhibit their differentiation in vitro and may participate in the regulation of adipose tissue development in vivo. Journal of Endocrinology (1992) 134, 163–168

Effects of transforming growth factor α (TGF-α) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells

1995 ◽  
Vol 132 (2) ◽  
pp. 242-248 ◽  
Author(s):  
Mariko Arai ◽  
Toshio Tsushima ◽  
Osamu Isozaki ◽  
Hiroshi Demura ◽  
Kazuo Shizume ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Dependent Manner ◽  
Camp Production ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Transforming Growth Factor Α ◽  
Iodine Metabolism ◽  
Factor Α

Arai M, Tsushima T, Isozaki 0, Demura H, Shizume K, Emoto N, Miyakawa M, Nozoe Y, Murakami H, Ohmura E. Effects of transforming growth factor α (TGF-α) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells. Eur J Endocrinol 1995;132:242–8. ISSN 0804–4643 Transforming growth factor α (TGF-α) is a potent mitogen that is similar structurally to epidermal growth factor (EGF). As EGF is a potent growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-α has similar effects using porcine thyroid cells in culture. Recombinant human TGF-α dose-dependently stimulated DNA synthesis of thyroid cells, with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and correlated with the ability to compete with EGF for receptor binding, suggesting that the action of TGF-α is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyrotropin (TSH) in the presence of TGF-α, TSH-induced iodide uptake was inhibited in a dose-dependent manner. The potency of TGF-α again was approximately 50% that of EGF. Transforming growth factor α did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake stimulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF-α. Thus, we conclude that TGF-α inhibits TSH-induced iodine metabolism largely by acting at the steps distal to cAMP production. Northern blot analysis revealed expression of TGF-α mRNA in porcine thyroid cells. These observations suggest that TGF-α acts as an autocrine modulator of growth and differentiated functions in porcine thyroid cells. T Tsushima, Department of Medicine 2, Tokyo Women's Medical College, Kawadacho 8–1, Shinjukuku, Tokyo 162, Japan

scholarly journals Transforming growth factor-α (TGF-α) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats

1992 ◽  
Vol 52 (6) ◽  
pp. 648-655 ◽  
Author(s):  
Norihiro Kokudo ◽  
Piyush C. Kothary ◽  
Frederic E. Eckhauser ◽  
Steven E. Raper
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Α ◽  
Factor Α
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