摘要:

AbstractIn the 10 years since its definition and characterization, TGF-βhas come to be accepted as the prototypical multifunctional peptide growth factor. Attempts to understand its mechanism of action on cells have resulted in conceptual advances in knowledge of the contextual nature of growth factor activities. These have included modulatory effects both of sets of growth factors and of the cellular environment, including extracellular matrix (Sporn and Roberts, 1990; Nathan and Sporn, 1991). Because of the breadth of the cellular targets and activities of TGF-βit is impossible to be comprehensive in review of its physiological roles. Rather, we will cover selected aspects with emphasis on physiological roles which might ultimately find clinical application. As much as possible, we will considerin vivoroles of TGF-βin the context of the inherent complexity of cell-matrix and cell-cell interactions characteristic of mixed cell populations, tissues, or organs.

ISSN:0897-7194    

DOI:10.3109/08977199309029129

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:0897-7194    

DOI:10.3109/08977199309029130

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractPancreatic cancer is an extremely aggressive malignancy. The factors allowing human pancreatic cancer cells to escape normal growth constraints are not known. However, it has been proposed that certain cancer cells may obtain a growth advantage as the result of a lack of responsiveness to negative growth regulators such as transforming growth factor-beta 1 (TGF-β1). We now show that two established pancreatic carcinoma cell lines, COLO 357 and PANC-I, are sensitive to growth inhibition by TGF-β1. The growth of COLO 357 cells is inhibited by 50% when incubated in the presence of TGF-β1 (5 ng/ml) under low serum conditions (0.5%). PANC-I cells are growth inhibited by 25% under the same conditions. In COLO 357 cells, but not PANC-I cells, TGF-β1 also causes a marked alteration in cell morphology. In both cell lines, TGF-β1 induces TGF-β1 mRNA levels in a time and dose-dependent manner. However, TGFβ1 does not increase the amount of TGF-β2 or TGF-β3 mRNA in these cells. In spite of its growth inhibitory effects, TGF-β1 fails to suppressc-mycmRNA levels. These findings suggest that TGF-β1 inhibits the growth of human pancreatic cancer cells and point to a significant dysfunction in the ability of TGF-β1 to suppressc-mycexpression in these cells.

ISSN:0897-7194    

DOI:10.3109/08977199309029131

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractThe sympathetic nervous system exerts a trophic-mitogenic effect on C-1300 mouse neuroblastoma. We now report that the trophic factor present in freshly excised sympathetic ganglia from newborn rats enhances survival and process formation of the cells of the septal region of the rat basal forebrain.

ISSN:0897-7194    

DOI:10.3109/08977199309029132

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractPreviously we have shown that epidermal growth factor (EGF) stimulates cardiac adenylyl cyclase and increases cAMP accumulation in the rat heart (Nair et al.,Biochem. J.264, 563–571, 1989). Moreover, we have shown that the stimulation of adenylyl cyclase by EGF in heart is mediated via activation of the stimulatory GTP binding regulatory protein Gsα(Nair et al.,J. Biol. Chem.265, 21317–21322, 1990). Since cAMP increases the beating rate of hearts, studies were performed to investigate the effects of EGF on mechanical function of the heart and the role of cAMP in mediating the cardiac effects of EGF. In isolated perfused rat hearts EGF (15 nM) decreased perfusion pressure, increased ventricular contractility and heart rate in a manner similar to that observed with theβ-adrenergic receptor agonist isoproterenol (10 nM). In the presence of the adenosine A1receptor agonist (-)-N6-(R-phenylisopropyl)-adenosine (PIA, 100 nM) which via activation of the inhibitory GTP binding protein Giinhibits adenylyl cyclase, the effects of EGF on cAMP accumulation in the heart were markedly attenuated. PIA also decreased the ability of EGF and isoproterenol to alter cardiac contractility and beating rate. However, PIA did not attenuate the increase in heart rate and contractility induced by theα-adrenergic agonist phenylephrine which does not stimulate cAMP accumulation in the heart. These data suggest that EGF alters cardiac function by increasing cellular cAMP accumulation.

ISSN:0897-7194    

DOI:10.3109/08977199309029133

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractImmunolocalization of basic fibroblast growth factor (bFGF) was investigated in NIH 3T3 cells transfected with a cDNA encoding for the 18 kD form of human bFGF (18 kD-bFGF) or with a bFGF cDNA encoding for both 18 kD-bFGF and NH2-terminal extended high molecular weight forms of bFGF (HMW-bFGFs). Nuclear and cytoplasmic bFGF-immunoreactivity was observed in both transfectants. Nuclear bFGF immunoreactivity was evenly distributed during interfase and associated with condensed chromosomes throughout the mitotic cycle. Cell fractionation, followed by Western blot analysis, confirmed the presence of 18 kD-bFGF and of HMW-bFGFs in the nucleus of transfected cells. Also, both 18-kD bFGF and HMW-bFGFs copurified with nuclear chromatin. After trypsin digestion, chromatin-bound bFGFs showed a rapid degradation of the nucleartargeting NH2-terminal extension of HMW-bFGFs which were converted to the 18 kD form. On the contrary, 18 kD-bFGF appeared to be trypsin-resistant when bound to nuclear chromatin or to isolated eukaryote DNA. Thus, our data indicate that: i) both 18 kD-bFGF and HMW-bFGFs localize into the nucleus of transfected NIH 3T3 cells and bind to nuclear chromatin; ii) the interaction of all bFGF isoforms with nuclear chromatin is mediated by one or more sequences present within the 18 kD form; iii) the chromatin-binding domain of HMW-bFGFs is distinct from their nuclear-targeting domain.

ISSN:0897-7194    

DOI:10.3109/08977199309029134

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractAcidic and basic fibroblast growth factors (aFGF, bFGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming growth factor type beta (TGFβ) are well-characterized growth regulators. Though there are reports of the effects of some of these factors on vascular cells, variability in the purity of growth factor preparations and differing cell culture conditions make comparison among the results difficult. Thus, a study employing homogeneous preparations of recombinant growth factors on well-characterized cell populations was conducted. Each of the factors was tested for its effect on the proliferation of cells derived from large and small blood vessels: aortic and capillary endothelial cells (EC), smooth muscle cells (SMC) and pericytes. Of the five growth factors only bFGF stimulated the proliferation of both large vessel and microvessel EC; aFGF was mitogenic for microvessel but not large vessel EC. Neither PDGF (AA, BB or AB) nor EGF had any effect on EC growth. TGF-βwas a potent inhibitor of both aortic and capillary EC proliferation with half maximal inhibition at concentrations as low as 0.05 and 0.25 ng/ml for microvessel and aortic EC, respectively. The FGFs were potent mitogens for the mural cells, SMC and pericytes. Likewise, PDGF was stimulatory for SMC and pericytes. The BB homodimer yielded the greatest degree of growth stimulation for both pericytes and SMC. In the case of SMC the AA homodimer stimulated small but significant growth and the effect of AB was intermediate to that of the homodimeric forms. On the other hand, neither the AA homodimer nor the heterodimer stimulated any significant increase in pericyte number. EGF was moderately mitogenic for both types of mural cells, reaching maximum stimulation at 100pg/ml of EGF. TGF-βwas inhibitory for SMC but not for pericyte proliferation. These data indicate both quantitative and qualitative differences between the responses of large and small vessel EC to the various growth factors and distinct differences in the responsiveness of SMC and pericytes to PDGF and to TGF-β.

ISSN:0897-7194    

DOI:10.3109/08977199309029135

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

AbstractNGFs have been isolated from the venom of many snakes. Here we report the isolation and the sequencing of a nearly full-length NGF cDNA from theBungarus multicinctusvenom gland cDNA library. The structure of the predicted krait precursor resembles that of cobra and of other animals, with a highly conserved mature NGF protein at the carboxy-terminus. Prepro part of the precursors are less conserved. The krait one possesses the presumptive 18 amino residues terminal signal sequence and the two long stretches corresponding to functional domains which are highly conserved alternating with large poorly conserved regions. We discuss particularities in the sequence of the precursor in the krait which may in part explain some earlier results obtained concerning this factor in the krait venom.

ISSN:0897-7194    

DOI:10.3109/08977199309029136

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor