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1.
Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains 总被引：18，自引：0，他引：18
M P Beckmann C Betsholtz C H Heldin B Westermark E Di Marco P P Di Fiore K C Robbins S A Aaronson 《Science (New York, N.Y.)》1988,241(4871):1346-1349
Human platelet-derived growth factor (PDGF) consists of two distinct but related polypeptide chains designated PDGF-A and PDGF-B. The gene encoding PDGF-B has given rise to the v-sis oncogene. In the present study the transforming activities of PDGF-A and PDGF-B genes are compared. The PDGF-A chain gene is markedly less efficient in inducing transformation than the PDGF-B gene under the influence of the same promoter. There are significant differences in the secretory and growth stimulating properties of the two chains. These properties appear to account for the much more potent transforming ability of the PDGF-B gene. These findings provide insights into biologic properties of a growth factor responsible for potent autocrine stimulation of abnormal cell proliferation. 相似文献
2.
Absence of TGF-beta receptors and growth inhibitory responses in retinoblastoma cells 总被引：22，自引：0，他引：22
A Kimchi X F Wang R A Weinberg S Cheifetz J Massagué 《Science (New York, N.Y.)》1988,240(4849):196-199
The responses of retinoblastoma tumor cells and normal retinal cells to various growth inhibitory factors were examined. Whereas fetal retinal cells were highly sensitive to the antimitogenic effects of transforming growth factor beta 1 (TGF-beta 1), retinoblastoma tumor cell lines were all resistant to this factor. Binding assays and affinity labeling of these cells with radioiodinated TGF-beta 1 revealed that the cells did not have TGF-beta receptors. The retinoblastoma cells lacked the three affinity-labeled proteins of 65, 95, and 300 kilodaltons typically seen in human cell lines and thus differed from normal retinal cells and from other types of neuroectodermal tumors that display the normal pattern of receptors. Loss of TGF-beta receptors, which is a rare event among tumor cells, may represent one mechanism through which these cells escape from negative control and form retinoblastomas. 相似文献
3.
Vascular endothelial growth factor is a secreted angiogenic mitogen 总被引：324，自引：0，他引：324
D W Leung G Cachianes W J Kuang D V Goeddel N Ferrara 《Science (New York, N.Y.)》1989,246(4935):1306-1309
Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF. 相似文献
4.
Human malignant cells secrete low molecular size proteins that attract peripheral blood monocytes and may be responsible for the accumulation of tumor-associated macrophages observed in vivo. Similar chemotactic proteins are secreted by cultured vascular smooth muscle cells. The predominant monocyte chemoattractants produced by tumor cells of differing origin were demonstrated to be related to smooth muscle cell-derived chemotactic factor. Thus, a single class of chemotactic proteins is produced by different cell types, which suggests a common mechanism for the recruitment of monocytes and macrophages. These results are significant in view of the potential of macrophages to affect tumor growth. 相似文献
5.
Kaposi's sarcoma cells: long-term culture with growth factor from retrovirus-infected CD4+ T cells 总被引：34，自引：0，他引：34
S Nakamura S Z Salahuddin P Biberfeld B Ensoli P D Markham F Wong-Staal R C Gallo 《Science (New York, N.Y.)》1988,242(4877):426-430
Studies of the biology and pathogenesis of Kaposi's sarcoma (KS) have been hampered by the inability to maintain long-term cultures of KS cells in vitro. In this study AIDS-KS-derived cells with characteristic spindle-like morphology were cultured with a growth factor (or factors) released by CD4+ T lymphocytes infected with human T-lymphotropic virus type I or II (HTLV-I or HTLV-II) or with human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2). Medium conditioned by HTLV-II-infected, transformed lines of T cells (HTLV-II CM) contained large amounts of this growth activity and also supported the temporary growth of normal vascular endothelial cells, but not fibroblasts. Interleukin-1 and tumor necrosis factor-alpha stimulated the growth of the KS-derived cells, but the growth was only transient and these could be distinguished from that in HTLV-II CM. Other known endothelial cell growth promoting factors, such as acidic and basic fibroblast growth factors and epidermal growth factor, did not support the long-term growth of the AIDS-KS cells. The factor released by CD4+ T cells infected with human retroviruses should prove useful in studies of the pathogenesis of KS. 相似文献
6.
Simian sarcoma virus--transformed cells secrete a mitogen identical to platelet-derived growth factor 总被引：28，自引：0，他引：28
Normal rat kidney (NRK) cells transformed by simian sarcoma virus (SSV) release into the culture medium a biologically active mitogen with properties identical to those of human platelet-derived growth factor (PDGF). Like PDGF, the growth factor derived from SSV-NRK cells was shown to be stable to heat and sensitive to reducing agents. It was capable of inhibiting binding of labeled PDGF to the receptor on human fibroblasts. It also stimulated the phosphorylation of the same membrane protein (185 kilodaltons) in isolated plasma membranes from human fibroblasts. Immunoprecipitation of metabolically labeled proteins released by SSV-NRK cells showed that a 34-kilodalton protein was specifically precipitated by antiserum to PDGF. Upon reduction, this protein had a molecular size of 17 kilodaltons. PDGF has been shown to consist of two 14- to 18-kilodalton proteins linked by disulfide bonds. 相似文献
7.
erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells 总被引：94，自引：0，他引：94
P P Di Fiore J H Pierce M H Kraus O Segatto C R King S A Aaronson 《Science (New York, N.Y.)》1987,237(4811):178-182
A wide variety of human tumors contain an amplified or overexpressed erbB-2 gene, which encodes a growth factor receptor-like protein. When erbB-2 complementary DNA was expressed in NIH/3T3 cells under the control of the SV40 promoter, the gene lacked transforming activity despite expression of detectable levels of the erbB-2 protein. A further five- to tenfold increase in its expression under influence of the long terminal repeat of Moloney murine leukemia virus was associated with activation of erbB-2 as a potent oncogene. The high levels of the erbB-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene. These findings demonstrate a new mechanism for acquisition of oncogenic properties by genes encoding growth factor receptor-like proteins and provide a functional basis for the role of their overexpression in the development of human malignancies. 相似文献
8.
The cancer stem cell hypothesis postulates that tumor growth is driven by a rare subpopulation of tumor cells. Much of the supporting evidence for this intriguing idea is derived from xenotransplantation experiments in which human leukemia cells are grown in immunocompromised mice. We show that, when lymphomas and leukemias of mouse origin are transplanted into histocompatible mice, a very high frequency (at least 1 in 10) of the tumor cells can seed tumor growth. We suggest that the low frequency of tumor-sustaining cells observed in xenotransplantation studies may reflect the limited ability of human tumor cells to adapt to growth in a foreign (mouse) milieu. 相似文献
9.
Association of human papillomavirus types 16 and 18 E6 proteins with p53 总被引：175，自引：0，他引：175
Human papillomavirus type 16 (HPV-16) is a DNA tumor virus that is associated with human anogenital cancers and encodes two transforming proteins, E6 and E7. The E7 protein has been shown to bind to the retinoblastoma tumor suppressor gene product, pRB. This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein. The ability of the E6 proteins from different human papillomaviruses to form complexes with p53 was assayed and found to correlate with the in vivo clinical behavior and the in vitro transforming activity of these different papillomaviruses. The wild-type p53 protein has tumor suppressor properties and has also been found in association with large T antigen and the E1B 55-kilodalton protein in cells transformed by SV40 and by adenovirus type 5, respectively, providing further evidence that the human papillomaviruses, the adenoviruses, and SV40 may effect similar cellular pathways in transformation. 相似文献
10.
Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation 总被引：1，自引：0，他引：1
Kratchmarova I Blagoev B Haack-Sorensen M Kassem M Mann M 《Science (New York, N.Y.)》2005,308(5727):1472-1477
Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics to comprehensively compare proteins that were tyrosine phosphorylated in response to EGF and PDGF and their associated partners. More than 90% of these signaling proteins were used by both ligands, whereas the phosphatidylinositol 3-kinase (PI3K) pathway was exclusively activated by PDGF, implicating it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences capable of changing cell fate. 相似文献
11.
The LDL receptor gene: a mosaic of exons shared with different proteins 总被引：112，自引：0，他引：112
The multifunctional nature of coated pit receptors predicts that these proteins will contain multiple domains. To establish the genetic basis for these domains (LDL) receptor. This gene is more than 45 kilobases in length and contains 18 exons, most of which correlate with functional domains previously defined at the protein level. Thirteen of the 18 exons encode protein sequences that are homologous to sequences in other proteins: five of these exons encode a sequence similar to one in the C9 component of complement; three exons encode a sequence similar to a repeat sequence in the precursor for epidermal growth factor (EGF) and in three proteins of the blood clotting system (factor IX, factor X, and protein C); and five other exons encode nonrepeated sequences that are shared only with the EGF precursor. The LDL receptor appears to be a mosaic protein built up of exons shared with different proteins, and it therefore belongs to several supergene families. 相似文献
12.
血管内皮生长因子研究进展 总被引：6，自引：0，他引：6
罗海玲 《甘肃农业大学学报》2001,36(3):243-258
血管内皮生长因子(Vascular Endothelial Growth Factor, VEGF)是一种由各种正常细胞或肿瘤细胞合成和分泌的糖蛋白。人类医学研究证明,VEGF有两种受体——KDR/FLK-1和FLT-1。VEGF与受体结合,具有促进血管内皮细胞的增生和提高微血管对大分子物质的通透性作用。人的VEGF 基因由8个外显子构成,主要有VEGF121、VEGF145、VEGF165、VEGF189和VEGF206等5个同型异构体。等电点的差异和肝素亲合力的差异可能是造成VEGF 生物活性差异的主要原因。 相似文献
13.
Interleukin-1 (IL-1) is a polypeptide cytokine that mediates many physiological responses to infection and inflammation and is a growth factor for certain mammalian cells. Virulent and avirulent clinical isolates of Escherichia coli were grown in culture media in the presence of human IL-1. IL-1 beta, but not tumor necrosis factor or IL-4, enhanced the growth of virulent, but not avirulent, E. coli. This enhancement was blocked by the IL-1 receptor antagonist (IL-1ra). Radiolabeled IL-1 bound to virulent but not avirulent E. coli in a specific and saturable fashion; IL-1ra inhibited this binding. Thus, human IL-1 may recognize a functional IL-1-like receptor structure on virulent E. coli and may be a virulence factor for bacterial pathogenicity. 相似文献
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Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro 总被引：118，自引：0，他引：118
B J Sugarman B B Aggarwal P E Hass I S Figari M A Palladino H M Shepard 《Science (New York, N.Y.)》1985,230(4728):943-945
Modulation of the growth of human and murine cell lines in vitro by recombinant human tumor necrosis factor-alpha (rTNF-alpha) and recombinant human interferon-gamma (rIFN-gamma) was investigated. rTNF-alpha had cytostatic or cytolytic effects on only some tumor cell lines. When administered together with rIFN-gamma, rTNF-alpha showed enhanced antiproliferative effects on a subset of the cell lines tested. In contrast to its effects on sensitive tumor cells, rTNF-alpha augmented the growth of normal diploid fibroblasts. Variations in the proliferative response induced by rTNF-alpha were apparently not due to differences in either the number of binding sites per cell or their affinity for rTNF-alpha. These observations indicate that the effects of rTNF-alpha on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo. 相似文献
16.
Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor 总被引：54，自引：0，他引：54
Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) are structurally related peptides. Purified human TGF-alpha produced in Escherichia coli and pure natural mouse EGF were compared for their ability to bind to target cells in vitro and to promote angiogenesis in the hamster cheek pouch bioassay. Both polypeptides were found to bind in vitro to several target cells, including endothelial cells, and to stimulate their DNA synthesis in an equipotent fashion. In vivo, however, TGF-alpha was more potent than EGF in promoting angiogenesis and, because TGF-alpha is known to be secreted by a variety of human tumors, it is suggested that this growth factor may contribute to tumor-induced angiogenesis. 相似文献
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Wang Z Shen D Parsons DW Bardelli A Sager J Szabo S Ptak J Silliman N Peters BA van der Heijden MS Parmigiani G Yan H Wang TL Riggins G Powell SM Willson JK Markowitz S Kinzler KW Vogelstein B Velculescu VE 《Science (New York, N.Y.)》2004,304(5674):1164-1166
Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention. 相似文献
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将茶氨酸为母体合成的茶氨酸衍生物茶氨酸溴香酰胺(TBrC)与茶氨酸作比较,评估茶氨酸溴香酰胺对人宫颈癌细胞体内外生长的抑制作用与其分子机制。应用MTT等方法检测不同浓度的TBrC对人宫颈癌细胞体外生长的影响,运用蛋白质印迹法检测解析这些人宫颈癌细胞中与凋亡和生长密切相关蛋白的表达和药物可能的作用靶点。此外,通过建立动物肿瘤模型,评价TBrC对荷瘤裸鼠人宫颈癌生长的抑制效果。实验结果显示,TBrC抑制人宫颈癌细胞体内外生长的活性超过其母体化合物茶氨酸多倍,对小鼠生长无明显毒性;TBrC作用的分子机制之一可能与抑制VEGFR1-Bcl-2/Bax信号传导通路相关。研究结果提示,TBrC具有广泛应用于临床治疗和(或)辅助治疗人宫颈癌和其他癌症的潜力。 相似文献