SKIN HYPERKERATOSIS AND PAPILLOMA FORMATION IN TRANSGENIC MICE EXPRESSING A RAS ONCOGENE FROM A SUPRABASAL KERATIN PROMOTER

SKIN HYPERKERATOSIS AND PAPILLOMA FORMATION IN TRANSGENIC MICE EXPRESSING A RAS ONCOGENE FROM A SUPRABASAL KERATIN PROMOTER
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DOI:
10.1016/0092-8674(90)90115-u
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发表时间:
1990-08-24
期刊:
影响因子:
64.5
通讯作者:
BALMAIN, A
BALMAIN, A
中科院分区:
生物学1区
文献类型:
--
作者:
BAILLEUL, B;SURANI, MA;BALMAIN, A

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基底上角蛋白 10 基因的启动子区域已被用来指导突变型人类 Harvey-ras 癌基因向小鼠表皮的分化细胞表达。转基因动物出现皮肤和前胃角化过度——已知这两个部位在体内表达高水平的角蛋白10多肽。随后,乳头状瘤出现在皮肤表面,最初出现在容易被咬或抓的部位,例如尾巴根部或耳朵后面。结果表明,这些转基因动物中涉及肿瘤发展的“第二个事件”是局部诱导轻微的创伤刺激。此外,因为H-ras转基因在基底上细胞中表达,所以似乎可以诱导离开干细胞区室的细胞在体内至少形成良性肿瘤。
The promoter region of the suprabasal keratin 10 gene had 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.