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在从基底层以上的角蛋白启动子表达ras癌基因的转基因小鼠中出现皮肤角化过度和乳头状瘤形成。

Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter.

作者信息

Bailleul B, Surani M A, White S, Barton S C, Brown K, Blessing M, Jorcano J, Balmain A

机构信息

Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow, Scotland.

出版信息

Cell. 1990 Aug 24;62(4):697-708. doi: 10.1016/0092-8674(90)90115-u.

DOI:10.1016/0092-8674(90)90115-u
PMID:1696852
Abstract

The promoter region of the suprabasal keratin 10 gene has been used to direct expression of a mutant human Harvey-ras oncogene to the differentiating cells of the mouse epidermis. Transgenic animals develop hyperkeratosis of the skin and forestomach--the two sites known to express high levels of the keratin 10 polypeptide in vivo. Papillomas subsequently develop on the skin surface, initially at sites subject to biting or scratching such as the base of the tail or behind the ears. The results suggest that the "second event" involved in tumor development in these transgenic animals is the local induction of a mild wounding stimulus. Furthermore, because the H-ras transgene is expressed in suprabasal cells, it appears that cells which have left the stem cell compartment can be induced to form at least benign tumors in vivo.

摘要

基底上层角蛋白10基因的启动子区域已被用于将突变的人类哈维 - ras癌基因定向表达至小鼠表皮的分化细胞中。转基因动物会出现皮肤和前胃的角化过度,这是已知在体内高水平表达角蛋白10多肽的两个部位。随后,皮肤表面会出现乳头状瘤,最初出现在易受咬伤或抓伤的部位,如尾巴根部或耳朵后面。结果表明,这些转基因动物肿瘤发生过程中涉及的“第二个事件”是局部诱导轻度创伤刺激。此外,由于H - ras转基因在基底上层细胞中表达,似乎已离开干细胞区室的细胞在体内可被诱导形成至少良性肿瘤。

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1
Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter.在从基底层以上的角蛋白启动子表达ras癌基因的转基因小鼠中出现皮肤角化过度和乳头状瘤形成。
Cell. 1990 Aug 24;62(4):697-708. doi: 10.1016/0092-8674(90)90115-u.
2
Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v-Ha-ras oncogene.靶向v-Ha-ras癌基因在转基因小鼠中诱导表皮增生、角化过度和乳头瘤形成。
Mol Carcinog. 1993;7(2):99-110. doi: 10.1002/mc.2940070208.
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v-Ha-ras-induced mouse skin papillomas exhibit aberrant expression of keratin K13 as do their 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate -induced analogues.v-Ha-ras诱导的小鼠皮肤乳头瘤与其7,12-二甲基苯并[a]蒽/12-O-十四烷酰佛波醇-13-乙酸酯诱导的类似物一样,呈现角蛋白K13的异常表达。
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Transcriptional control of high molecular weight keratin gene expression in multistage mouse skin carcinogenesis.多阶段小鼠皮肤致癌过程中高分子量角蛋白基因表达的转录调控
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Human keratin-1.bcl-2 transgenic mice aberrantly express keratin 6, exhibit reduced sensitivity to keratinocyte cell death induction, and are susceptible to skin tumor formation.人角蛋白-1.bcl-2转基因小鼠异常表达角蛋白6,对角质形成细胞死亡诱导的敏感性降低,且易发生皮肤肿瘤。
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The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted.由突变型H-ras转基因表达诱导的皮肤肿瘤的恶性能力取决于所靶向的细胞类型。
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VEGF/VPF overexpression in skin of transgenic mice induces angiogenesis, vascular hyperpermeability and accelerated tumor development.转基因小鼠皮肤中VEGF/VPF的过表达会诱导血管生成、血管通透性增加并加速肿瘤发展。
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Cooperation between Ha-ras and fos or transforming growth factor alpha overcomes a paradoxic tumor-inhibitory effect of p53 loss in transgenic mouse epidermis.Ha-ras与fos或转化生长因子α之间的合作克服了转基因小鼠表皮中p53缺失所产生的反常肿瘤抑制效应。
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Cooperation between v-fos and v-rasHA induces autonomous papillomas in transgenic epidermis but not malignant conversion.v-fos与v-rasHA之间的合作可在转基因表皮中诱导自主性乳头瘤,但不会导致恶性转化。
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Severe follicular hyperplasia and spontaneous papilloma formation in transgenic mice expressing the neu oncogene under the control of the bovine keratin 5 promoter.在牛角蛋白5启动子控制下表达neu癌基因的转基因小鼠中出现严重的毛囊增生和自发性乳头瘤形成。
Mol Carcinog. 1998 Jan;21(1):2-12.

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