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猿猴病毒40转化的卡波西肉瘤衍生细胞的细胞化学和分子特性:成纤维细胞生长因子家族一员分泌的证据

Cytochemical and molecular properties of simian virus 40 transformed Kaposi's sarcoma-derived cells: evidence for the secretion of a member of the fibroblast growth factor family.

作者信息

Werner S, Hofschneider P H, Stürzl M, Dick I, Roth W K

机构信息

Department of Virus Research, Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany.

出版信息

J Cell Physiol. 1989 Dec;141(3):490-502. doi: 10.1002/jcp.1041410307.

Abstract

Contact-inhibited Kaposi's sarcoma-derived cells (KS cells) were transfected with Simian Virus 40 (SV40) DNA. Transformed cells (SV-KSC) were selected for their capacity to form foci on monolayers of the low-malignant KS cells. Isolated SV-KSC foci were found to contain integrated SV40 DNA sequences and to express SV40 large T-antigen. Several differentiation properties of KS cells are retained in the SV40 transformants, e.g., expression of vimentin and the endothelial cell marker BMA 120. In contrast to the maternal KS cells, SV-KSC are capable of growing in platelet-derived growth factor (PDGF)-depleted platelet-poor-plasma serum (PPPS) and in soft agar. However, they are not tumorigenic in nude mice. Expression of the oncogenes c-myc, c-N-ras, c-Ha-ras, and p53 is significantly elevated in SV-KSC, whereas c-fos and c-erb B expression is comparable to that of KS cells and fibroblasts. Conditioned medium from SV-KSC can substitute for PDGF when PDGF-dependent, nontransformed KS cells are grown in PPPS. Biochemical analysis of the SV-KSC supernatant and PDGF A and B mRNA expression analysis provide evidence that the mitogenic activity is not due to a PDGF-like growth factor. On the other hand, there is evidence to indicate that the SV-KSC mitogen is a member of the fibroblast growth factor family. SV-KSC represent an interesting model system for the study of different degrees of malignancy of cultured mesenchymal cells and especially provide an important source for the isolation of a potent growth factor for KS cells and other mesenchymal cells in vitro.

摘要

将猿猴病毒40(SV40)DNA转染至接触抑制的卡波西肉瘤衍生细胞(KS细胞)。选择转化细胞(SV-KSC)是因为它们能够在低恶性KS细胞单层上形成集落。发现分离出的SV-KSC集落含有整合的SV40 DNA序列并表达SV40大T抗原。KS细胞的几种分化特性在SV40转化体中得以保留,例如波形蛋白和内皮细胞标志物BMA 120的表达。与亲代KS细胞不同,SV-KSC能够在血小板衍生生长因子(PDGF)缺失的少血小板血浆血清(PPPS)中以及软琼脂中生长。然而,它们在裸鼠中不具有致瘤性。癌基因c-myc、c-N-ras、c-Ha-ras和p53在SV-KSC中的表达显著升高,而c-fos和c-erb B的表达与KS细胞和成纤维细胞相当。当依赖PDGF的未转化KS细胞在PPPS中生长时,SV-KSC的条件培养基可以替代PDGF。对SV-KSC上清液的生化分析和PDGF A和B mRNA表达分析提供了证据,表明促有丝分裂活性不是由类似PDGF的生长因子引起的。另一方面,有证据表明SV-KSC促有丝分裂原是成纤维细胞生长因子家族的成员。SV-KSC代表了一个有趣的模型系统,用于研究培养的间充质细胞不同程度的恶性肿瘤,尤其为体外分离一种对KS细胞和其他间充质细胞有效的生长因子提供了重要来源。

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