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首页> 外文期刊>Journal of Cellular Physiology >Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential drug resistance and amplification potential.
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Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential drug resistance and amplification potential.

机译：过度的18 kDa, 22/24 kDa FGF-2亚型导致微分耐药性和放大的潜力。

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摘要

We investigated the role of low molecular weight (LMW) and high molecular weight (HMW) isoforms of basic fibroblast growth factor 2 (FGF-2) in the expression of transformation-related phenotypic alterations, drug sensitivity modulation, and gene amplification potential. For this purpose, we used NIH 3T3 and A31 cells transfected with different cDNA FGF-2 constructs allowing expression of the different proteins. Both cell lines showed marked phenotypic alterations when expressing the LMW FGF-2 or the four HMW FGF-2 isoforms: they acquired a transformed morphology, grew at higher saturation densities in 10% serum, and exhibited anchorage-independent growth and increased invasive potential. However, HMW FGF-2-expressing cells also grew in 1% serum and their invasive potential was lower than in cells expressing all FGF-2 forms or LMW FGF-2 alone. We have grown the different cell lines under a selective pressure of N-(phosphonacetyl)-l-aspartate (PALA), a drug which specifically inhibits the aspartate transcarbamylase activity of the multifunctional carbamyl-P-synthetase/aspartate transcarbamylase/dihydro-orotase genes (CAD) enzyme (and thus inhibits de novo pyrimidine biosynthesis) and selects for cells with amplified copies of the CAD gene. Our results demonstrate that aberrant expression of the LMW FGF-2 and/or HMW FGF-2 isoforms differently modulates drug resistance and gene amplification properties in the NIH 3T3 and A31 cell lines by differential amplification of the CAD gene. Coexpression of all isoforms appears to be necessary to obtain cumulative effects and nuclear-targeted HMW FGF-2 has a pivotal role in such a cooperation.
机译：我们研究了低分子量的角色(流明瓦)和高分子量(高分子量)的亚型基本成纤维细胞生长因子2 (FGF-2)与转换相关的表型的表达改变、药物敏感性调制基因扩增的潜力。我们用NIH 3 t3和A31细胞转染不同的cDNA FGF-2构造允许表达不同的蛋白质。行显示明显的表型变化表达了流明瓦FGF-2或四高分子量FGF-2亚型:他们获得了转化形态,增长速度更高的饱和密度在10%血清,和anchorage-independent增长和展出增加入侵潜力。血清和FGF-2-expressing细胞也增长1%他们入侵潜力低于细胞表达所有FGF-2形式或流明瓦FGF-2孤单。已经下不同的细胞系选择性的压力(N) - phosphonacetyl -l-aspartate的评比,一种药物专门抑制天冬氨酸盐氨甲酰基转移酶活动的多功能carbamyl-P-synthetase /天冬氨酸盐transcarbamylase / dihydro-orotase基因(发援会)酶(从而抑制新创嘧啶细胞的生物合成)和选择放大的CAD基因副本。证明流明瓦的异常表达FGF-2和/或高分子量FGF-2亚型不同调节耐药性和基因扩增属性在NIH 3 t3和A31细胞系差动放大的CAD基因。Coexpression亚型似乎有必要获得累积效应和nuclear-targeted高分子量FGF-2有关键作用这样的合作。

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