Bailleul B, Surani M A, White S, Barton S C, Brown K, Blessing M, Jorcano J, Balmain A
Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow, Scotland.
Cell. 1990 Aug 24;62(4):697-708. doi: 10.1016/0092-8674(90)90115-u.
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.
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。