Radosevich J A, Combs S G, Ma Y, Lee I, Gould V E, Thor A, Schlom J, Carney W P, Rosen S T
Northwestern University, Veterans Administration, Lakeside Medical Center, Department of Medicine, Chicago, Illinois 60611.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;56(5):337-44. doi: 10.1007/BF02890035.
In this report we describe the expression of the ras proto-oncogene p21 protein in various tissues during normal fetal development. Conventional, formalin fixed and paraffin-embedded sections of normal organs were examined from fetuses ranging 9 to 42 weeks of gestation. Immunohistochemical localization of ras p21 was accomplished using the broadly reactive, mouse monoclonal antibodies RAP-5 and Y13-259. The monoclonal antibody DWP, which is specific for a mutated form of ras p21 having a valine/cysteine at amino acid position 12, was also used. Detectable expression of the p21 protein was seen at different time periods during fetal development depending on the tissue. The expression of ras p21 (as detected by RAP-5 and Y13-259) was noted in a wide range of cell types and tissues; intense immunostaining was noted in epithelial cells of the gastrointestinal tract, exocrine and endocrine pancreas, renal tubules and transitional urotheliem, as well as in other tissues. This immunostaining generally, but not invariably, corresponded with patterns previously reported in benign and/or malignant neoplasms of adult tissues. In most instances ras p21 expression, when present, occurred during periods of rapid growth in given organ systems. However, some actively proliferating fetal tissues such as thymus and spleen, failed to express detectable ras p21 suggesting that factors other than cell cycle may influence its expression. No reactivity with DWP was noted in any of the tissues, suggesting that the mutated forms detected by this monoclonal antibody are not expressed during normal human embryogenesis. These data show that there is regulated expression, and broad distribution of this gene product in normal developing human fetal tissue.
在本报告中，我们描述了原癌基因ras p21蛋白在正常胎儿发育过程中在各种组织中的表达情况。对妊娠9至42周胎儿的正常器官常规福尔马林固定石蜡包埋切片进行了检查。使用具有广泛反应性的小鼠单克隆抗体RAP-5和Y13-259完成了ras p21的免疫组织化学定位。还使用了单克隆抗体DWP，它对在氨基酸位置12处具有缬氨酸/半胱氨酸的ras p21突变形式具有特异性。根据组织的不同，在胎儿发育的不同时期可见p21蛋白的可检测表达。ras p21的表达（通过RAP-5和Y13-259检测）在多种细胞类型和组织中被观察到；在胃肠道、外分泌和内分泌胰腺、肾小管和移行性尿路上皮以及其他组织的上皮细胞中观察到强烈的免疫染色。这种免疫染色一般但并非总是与先前在成人组织的良性和/或恶性肿瘤中报道的模式一致。在大多数情况下，ras p21表达（如果存在）发生在特定器官系统快速生长的时期。然而，一些活跃增殖的胎儿组织如胸腺和脾脏未能表达可检测到的ras p21，这表明除细胞周期外的其他因素可能影响其表达。在任何组织中均未观察到与DWP的反应性，这表明该单克隆抗体检测到的突变形式在正常人类胚胎发育过程中不表达。这些数据表明，该基因产物在正常发育的人类胎儿组织中有调节表达且分布广泛。
