Real-time reverse transcription-PCR quantification of vascular endothelial growth factor splice variants.

Real-time reverse transcription-PCR quantification of vascular endothelial growth factor splice variants.
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DOI:
10.1373/clinchem.2004.046987
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发表时间:
2005-08
期刊:
影响因子:
9.3
通讯作者:
Eleni Zygalaki;A. Stathopoulou;C. Kroupis;L. Kaklamanis;Z. Kyriakides;D. Kremastinos;E. Lianidou
Eleni Zygalaki;A. Stathopoulou;C. Kroupis;L. Kaklamanis;Z. Kyriakides;D. Kremastinos;E. Lianidou
中科院分区:
医学1区
文献类型:
--
作者:
Eleni Zygalaki;A. Stathopoulou;C. Kroupis;L. Kaklamanis;Z. Kyriakides;D. Kremastinos;E. Lianidou

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血管内皮生长因子 (VEGF) 是一种内皮细胞特异性有丝分裂原,也是多种生理和病理过程中血管生成的关键调节剂 (1)。人类 VEGF 基因位于染色体 6p21.3 上,由 8 个外显子 (2)(3) 组成。 VEGF 基因的选择性外显子剪接产生各种剪接变体(下标表示信号序列切割后的氨基酸数量):VEGF206、VEGF189、VEGF183、VEGF165、VEGF148、VEGF145 和 VEGF121 (4)(5)(6)(7)(8)。外显子 1-5 和 8 在所有变体中均保留,而外显子 6a、6b 和 7 的存在或缺失则区分变体。 VEGF121 缺乏这些外显子 (4),VEGF165 包含外显子 7 编码序列 (4),VEGF148 与 VEGF165 具有相同的氨基酸序列,除了外显子 7 末端有 35 bp 长的缺失 (5)。 VEGF189 包含外显子 6a 和 7 (4),而在 VEGF183 中,外显子 6a 的最后 18 bp 缺失 (6)。 VEGF145 包含外显子 6a,但缺少外显子 7 (7)。 VEGF206 是全长形式,除了外显子 6a 和 7 之外,还包含来自内含子 3、外显子 6b、邻近外显子 6a 的 51 bp 部分 (8)。 VEGF 亚型的肝素和硫酸乙酰肝素结合能力以及受体亲和力有所不同 (9),但其确切的生物学作用仍不清楚。大多数 VEGF 产生细胞似乎优先表达 VEGF121、VEGF165 和 VEGF189 (4)。 VEGF183 具有广泛的组织分布,并且可能由于与 VEGF189 混淆而未被更早地检测到 (6)。 VEGF145 是源自女性生殖系统癌的几种细胞系产生的主要变体之一(7 …
Vascular endothelial growth factor (VEGF) is an endothelial cell–specific mitogen and a key regulator of angiogenesis in a variety of physiologic and pathologic processes (1). The human gene for VEGF resides on chromosome 6p21.3 and is organized into 8 exons (2)(3). Alternative exon splicing of the VEGF gene produces various splice variants (subscripts denote the number of amino acids after signal sequence cleavage): VEGF206, VEGF189, VEGF183, VEGF165, VEGF148, VEGF145, and VEGF121 (4)(5)(6)(7)(8). Exons 1–5 and 8 are preserved in all variants, whereas the presence or absence of exons 6a, 6b, and 7 distinguish variants. VEGF121 lacks these exons (4), VEGF165 contains the exon 7-encoded sequence (4), and VEGF148 has the same amino acid sequence as VEGF165 apart from a 35-bp–long deletion at the end of exon 7 (5). VEGF189 contains exons 6a and 7 (4), whereas in VEGF183 the final 18 bp of exon 6a are missing (6). VEGF145 contains exon 6a but lacks exon 7 (7). VEGF206 is the full-length form containing, in addition to exons 6a and 7, a 51-bp part from intron 3, exon 6b, neighboring exon 6a (8). VEGF isoforms differ in their heparin and heparan sulfate binding capacities as well as in their receptor affinities (9), but their exact biological roles remain unclear. Most VEGF-producing cells appear to preferentially express VEGF121, VEGF165, and VEGF189 (4). VEGF183 has a wide tissue distribution and may have not been detected earlier because of confusion with VEGF189 (6). VEGF145 is one of the main variants produced by several cell lines derived from carcinomas of the female reproductive system (7 …