Fynan T M, Morgan D, Yuspa S H, Longley B J, Zhou Z L, Reiss M
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520.
Cell Growth Differ. 1994 Dec;5(12):1293-300.
Somatic cell hybrid cell lines derived from the fusion of human squamous carcinoma cells (FaDu-Hyg) with human keratinocytes were used to examine the relationships between cell differentiation and tumorigenicity. Treatment of the parental keratinocytes or the two hybrid cell lines with the combination of calcium and fetal bovine serum increased the expression of the envelope precursor, involucrin, 4- to 8-fold, whereas it remained unchanged in FaDu-Hyg cells. Similarly, calcium- and serum-treated keratinocytes and the two hybrid cell lines displayed a 7- to 13-fold increase of the activity of membrane-associated type I transglutaminase, whereas transglutaminase activity in FaDu-Hyg cells did not change appreciably. FaDu-Hyg cells were tumorigenic in vivo, but tumorigenicity was suppressed in both hybrid cell lines. Analysis of additional tumor cell lines indicated that the expression of transglutaminase I and involucrin are under separate genetic control and that loss of transglutaminase activity can result either from a lack of protein or from a defect in the activation step. Thus, keratinization of squamous epithelial cells appears to be controlled by several different recessive genes, which cosegregate with but are probably only partly identical with the genes that suppress tumor formation in vivo.
源自人鳞状癌细胞（FaDu-Hyg）与人角质形成细胞融合的体细胞杂交细胞系被用于研究细胞分化与致瘤性之间的关系。用钙和胎牛血清联合处理亲代角质形成细胞或两种杂交细胞系，包膜前体兜甲蛋白的表达增加了4至8倍，而在FaDu-Hyg细胞中其表达保持不变。同样，经钙和血清处理的角质形成细胞及两种杂交细胞系，膜相关I型转谷氨酰胺酶的活性增加了7至13倍，而FaDu-Hyg细胞中的转谷氨酰胺酶活性没有明显变化。FaDu-Hyg细胞在体内具有致瘤性，但两种杂交细胞系的致瘤性均受到抑制。对其他肿瘤细胞系的分析表明，转谷氨酰胺酶I和兜甲蛋白的表达受不同的基因控制，转谷氨酰胺酶活性的丧失可能是由于蛋白质缺乏或激活步骤存在缺陷。因此，鳞状上皮细胞的角质化似乎受几个不同的隐性基因控制，这些基因与体内抑制肿瘤形成的基因共分离，但可能只是部分相同。
