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对包括在MCF-7乳腺癌细胞中表达的四种成纤维细胞生长因子受体(FGF受体)mRNA在内的酪氨酸激酶mRNA的分析。

Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs expressed in MCF-7 breast-cancer cells.

作者信息

Lehtola L, Partanen J, Sistonen L, Korhonen J, Wärri A, Härkönen P, Clarke R, Alitalo K

机构信息

Department of Pathology, University of Helsinki, Finland.

出版信息

Int J Cancer. 1992 Feb 20;50(4):598-603. doi: 10.1002/ijc.2910500419.

DOI:10.1002/ijc.2910500419
PMID:1311287
Abstract

The MCF-7 cell line is a hormone-responsive human breast-cancer cell line, which has been extensively used in studies of estrogen regulation of cell growth. These studies have indicated that the growth stimulation of the MCF-7 cells by estrogens may be effected by an autocrine mechanism involving several growth factors, such as EGF, TGF alpha and IGF-I and their receptors. We have amplified and cloned tyrosine-kinase-related sequences from the MCF-7 cell mRNA using the polymerase chain reaction and characterized the partial cDNAs obtained by nucleic acid sequencing. Nine tyrosine kinase cDNAs and one serine/threonine kinase cDNA were identified among the amplified sequences. Four different tyrosine kinase genes encoding receptors for fibroblast growth factors (FGFs) were found to be expressed by the MCF-7 cells. In addition, differences were observed in the expression of these members of FGF receptor family in different breast-cancer cells. A putative tyrosine-kinase receptor and a novel serine/threonine kinase were preferentially expressed in estrogen-responsive tumor cell lines. However, no estrogen-dependent regulation of any of the novel tyrosine-kinase receptor mRNAs was found in any of the cell lines including the MCF-7 or ZR-75-I cells, where the expression of the neu proto-oncogene mRNA was decreased during estrogen treatment. The expression of several FGF receptors by breast-cancer cells suggests that FGFs may be involved in their growth regulation and tumorigenesis.

摘要

MCF - 7细胞系是一种激素反应性人乳腺癌细胞系,已广泛用于雌激素对细胞生长调节的研究。这些研究表明,雌激素对MCF - 7细胞的生长刺激可能通过一种自分泌机制实现,该机制涉及多种生长因子,如表皮生长因子(EGF)、转化生长因子α(TGFα)和胰岛素样生长因子 - I(IGF - I)及其受体。我们利用聚合酶链反应从MCF - 7细胞mRNA中扩增并克隆了酪氨酸激酶相关序列,并通过核酸测序对获得的部分cDNA进行了表征。在扩增序列中鉴定出9个酪氨酸激酶cDNA和1个丝氨酸/苏氨酸激酶cDNA。发现MCF - 7细胞表达4种不同的编码成纤维细胞生长因子(FGFs)受体的酪氨酸激酶基因。此外,在不同的乳腺癌细胞中观察到FGF受体家族这些成员的表达存在差异。一种推定的酪氨酸激酶受体和一种新型丝氨酸/苏氨酸激酶在雌激素反应性肿瘤细胞系中优先表达。然而,在包括MCF - 7或ZR - 75 - I细胞在内的任何细胞系中,均未发现任何新型酪氨酸激酶受体mRNA的雌激素依赖性调节,在雌激素处理期间,这些细胞系中neu原癌基因mRNA的表达会降低。乳腺癌细胞对几种FGF受体的表达表明,FGFs可能参与其生长调节和肿瘤发生。

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