Gimenez-Conti I B, Shin D M, Bianchi A B, Roop D R, Hong W K, Conti C J, Slaga T J
University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957.
Cancer Res. 1990 Jul 15;50(14):4441-5.
This study was undertaken to explore the expression of keratins in the hamster cheek pouch carcinogenesis model, using monospecific keratin antibodies and a technique that allows immunoblotting analysis of tissues embedded in paraffin. Changes in keratin expression were correlated with histopathological changes and with the expression of the enzyme gamma-glutamyl transpeptidase. The right cheek pouch of 20 male golden Syrian hamsters was treated with 0.5% 7,12-dimethylbenz[a]anthracene for 16 weeks. As previously described by other laboratories, this treatment resulted in hyperplastic and dysplastic lesions and benign and malignant tumors. The keratins assayed in this study were K14 (Mr 55,000), K1 (Mr 67,000), and K13 (Mr 47,000). The normal hamster cheek pouch epithelium expressed K14 in the basal layer and K13 in the suprabasal and differentiated layers, whereas K1 was not detected by either immunohistochemistry or immunoblotting. Concomitant with 7,12-dimethylbenz[a]anthracene-induced hyperplasia, there were some topographical alterations in the distribution of K14. In this case, K14 was no longer restricted to the basal layer but was also expressed in differentiated cells. The same pattern was also observed in dysplastic lesions and in squamous cell carcinoma. Furthermore, expression of the K13 differentiation-associated keratin was preserved in this hyperplastic epithelium during all the stages of carcinogenesis, including either anaplastic or differentiated areas. In contrast, after 2 weeks of 7,12-dimethylbenz[a]anthracene treatment, K1 expression started as a weak and patchy pattern in suprabasal cells, becoming stronger and more homogeneous at 8 and 16 weeks of treatment. However, K1 was almost absent in squamous cell carcinoma, where only small very well differentiated areas were stained. We also observed gamma-glutamyl transpeptidase-positive foci in earlier stages of carcinogenesis, concomitant with the expression of the K1 keratin. However, it was not possible to find a perfect topographical correspondence between the two events. Alterations in the pattern of keratin expression appear to be a common feature during the development of squamous cell carcinoma in different systems and could be an excellent tool to study carcinogenesis and chemoprevention.
本研究旨在利用单特异性角蛋白抗体及一种可对石蜡包埋组织进行免疫印迹分析的技术，探究仓鼠颊囊癌变模型中角蛋白的表达情况。角蛋白表达的变化与组织病理学变化以及γ-谷氨酰转肽酶的表达相关。对20只雄性金黄叙利亚仓鼠的右侧颊囊用0.5%的7,12-二甲基苯并[a]蒽处理16周。正如其他实验室之前所描述的，这种处理导致了增生性和发育异常性病变以及良性和恶性肿瘤。本研究中检测的角蛋白为K14（分子量55,000）、K1（分子量67,000）和K13（分子量47,000）。正常仓鼠颊囊上皮在基底层表达K14，在基底上层和分化层表达K13，而通过免疫组织化学或免疫印迹均未检测到K1。伴随7,12-二甲基苯并[a]蒽诱导的增生，K14的分布出现了一些拓扑学改变。在这种情况下，K14不再局限于基底层，也在分化细胞中表达。在发育异常性病变和鳞状细胞癌中也观察到了相同的模式。此外，在癌变的所有阶段，包括间变或分化区域，与K13分化相关的角蛋白在这种增生性上皮中均得以保留。相反，在7,12-二甲基苯并[a]蒽处理2周后，K1在基底上层细胞中开始呈微弱且散在的模式表达，在处理8周和16周时变得更强且更均匀。然而，在鳞状细胞癌中K1几乎缺失，仅极小的高分化区域被染色。我们还在癌变的早期阶段观察到γ-谷氨酰转肽酶阳性灶，与K1角蛋白的表达相伴。然而，无法在这两个事件之间找到完美的拓扑学对应关系。角蛋白表达模式的改变似乎是不同系统中鳞状细胞癌发生过程中的一个共同特征，并且可能是研究癌变和化学预防的一个极好工具。
