Heyden A, Lützow-Holm C, Clausen O P, Brandtzaeg P, Huitfeldt H S
Laboratory of Immunohistochemistry and Immunopathology (LIIPAT), National Hospital, Oslo, Norway.
Epithelial Cell Biol. 1994 Jul;3(3):96-101.
Biosynthesis of the hyperproliferation-associated keratins K6 and K16 was studied in mouse epidermis following a single topical application of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). An epidermal cell cohort was followed by pulse-labelling with the thymidine analogue 5-bromodeoxyuridine (BrdUrd). Mice were injected intraperitoneally with BrdUrd 1 h before a single topical application of TPA. TPA induced regenerative epidermal hyperplasia with hyperproliferation and shortened suprabasal transit time. The BrdUrd-labelled cell cohort was followed for 96 h after TPA-treatment by two-colour immunofluorescence staining with antibodies to BrdUrd, keratin K6 and K16. In control animals, K6 and K16 were found only in the hair follicles. K6 expression was immediately induced in all epidermal cell layers of TPA-treated epidermis, including actively replicating cells and it was expressed during the whole observation period. K16 was only present in post-mitotic cells and was transiently expressed 8-72 h after TPA treatment. Our results suggest that the expression of K6 and K16 is less restricted by cellular replication than the normally occurring K1 and K10 keratins.
在单次局部应用肿瘤启动子12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯(TPA)后,研究了小鼠表皮中与过度增殖相关的角蛋白K6和K16的生物合成。通过用胸苷类似物5 - 溴脱氧尿苷(BrdUrd)进行脉冲标记来追踪表皮细胞群体。在单次局部应用TPA前1小时,给小鼠腹腔注射BrdUrd。TPA诱导再生性表皮增生,伴有过度增殖和缩短的基底层以上转运时间。在TPA处理后,通过用抗BrdUrd、角蛋白K6和K16的抗体进行双色免疫荧光染色,对BrdUrd标记的细胞群体追踪96小时。在对照动物中,仅在毛囊中发现K6和K16。在TPA处理的表皮的所有表皮细胞层中,包括活跃复制的细胞,K6表达立即被诱导,并且在整个观察期内都有表达。K16仅存在于有丝分裂后的细胞中,并且在TPA处理后8 - 72小时短暂表达。我们的结果表明,与正常表达的角蛋白K1和K10相比,K6和K16的表达受细胞复制的限制较小。