Comparative expression of novel vascular endothelial growth factor/vascular permeability factor transcripts in skin, papillomas, and carcinomas of v-Ha-ras Tg.AC transgenic mice and FVB/N mice.
Comparative expression of novel vascular endothelial growth factor/vascular permeability factor transcripts in skin, papillomas, and carcinomas of v-Ha-ras Tg.AC transgenic mice and FVB/N mice.
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v-Ha-ras Tg.AC 转基因小鼠和 FVB/N 小鼠的皮肤、乳头状瘤和癌中新型血管内皮生长因子/血管通透性因子转录物的比较表达。
DOI：
10.1006/bbrc.1998.8787
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Robertson,FM
中科院分区：
文献类型：
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作者：
Tober,KL;Cannon,RE;Spalding,JW;Oberyszyn,TM;Parrett,ML;Rackoff,AI;Oberyszyn,AS;Tennant,RW;Robertson,FM
在人类实体瘤中最常见的变化之一是therasoncogene突变，该突变与血管内皮生长因子/血管渗透因子(VEGF/VPF)等血管生成生长因子的产生有关。以v-Ha-rasTg.AC转基因小鼠和FVB/N近交系小鼠为研究对象，研究了多阶段皮肤癌变过程中主要脏器及皮肤、乳头状瘤和癌组织中特异性VEGF/VPF转录本的表达模式。在两个品系的小鼠的皮肤和主要器官中都发现了3个VEGF/VPF转录本的组成性表达，它们的大小和序列与先前报道的小鼠VEGF120、VEGF164和VEGF188的大小和序列一致，VEGF120的大小为331，VEGF164的大小为333，VEGF188的大小为407。在两个小鼠品系的皮肤和主要组织中也发现了之前未报道的第四个小鼠转录本，与大鼠VEGF144相对应，其BP大小为404。此外，从v-Ha-rasTg.AC小鼠分离的乳头状瘤和癌组织中也存在一个独特的425bpVEGF206转录本，该转录本对应于人VEGF206在心、肺、肝、肾、脑等高度血管化的组织中存在。相反，VEGF205仅存在于来自FVB/N小鼠的肿瘤中。从RT-PCR分析定义的五个VEGF/VPF多肽中的每一个的多肽序列中产生的抗体证实了这五个多肽的存在，并证实了小鼠VEGF205多肽在v-Ha-rasTg.AC小鼠的乳头状瘤和癌中选择性表达。这些结果表明，在多阶段癌变过程中，小鼠VEGF/VPF基因存在显著的选择性剪接，从而导致4种共同表达的VEGF转录本。此外，这些研究还发现了第五个血管内皮生长因子转录本和多肽，它们似乎与v-Ha-ras的存在有关。
One of the most frequently detected changes in human solid tumors is the mutation of therasoncogene, which has been associated with production of angiogenic growth factors such as vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Using the v-Ha-rasTg.AC transgenic mice and the background FVB/N strain of inbred mice, the pattern of expression of specific VEGF/VPF transcripts was characterized in major organs and in skin, papillomas, and carcinomas during multi-stage skin carcinogenesis. Three VEGF/VPF transcripts were found to be constitutively expressed in skin as well as the major organs in both mouse strains, which corresponded in size and sequence to previously reported murine VEGF120with a bp size of 331, VEGF164with a bp size of 333, and VEGF188with a bp size of 407. A previously unreported fourth murine transcript was also detected in skin and major tissues from both mouse strains which corresponded to rat VEGF144, with a bp size of 404. In addition, a unique 425 bp VEGF transcript which corresponded to human VEGF206was present in highly vascularized tissues including heart, lung, liver, kidney, brain, as well in papillomas and carcinomas isolated from v-Ha-rasTg.AC mice. In contrast, VEGF205was present only in carcinomas derived from FVB/N mice. An antibody generated from a peptide sequence designed to detect each of the five VEGF/VPF peptides defined by RT-PCR analysis confirmed the existence of these five peptides and confirmed that the murine VEGF205peptide was selectively expressed in papillomas and carcinomas derived from v-Ha-rasTg.AC mice. These results demonstrate that there is significant alternative splicing of the murine VEGF/VPF gene during multi-stage carcinogenesis, which results in four commonly expressed VEGF transcripts. In addition, these studies identified a fifth VEGF transcript and peptide at the later stages of tumor promotion and in progression which appears to be linked to the presence of v-Ha-ras.