Adleff V, Rácz K, Szende B, Tóth M, Moldvay J, Varga I, Bezzegh A, Szegedi Z, Gláz E
Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary.
J Steroid Biochem Mol Biol. 1998 Jul;66(1-2):27-33. doi: 10.1016/s0960-0760(98)00004-1.
The presence of p53 and tissue transglutaminase (tTG) gene expressions was investigated in human normal and pathologic adrenal tissues with two aims (1) to determine the tissue content of p53 protein, its messenger ribonucleic acid (mRNA) and, especially, tTG mRNA which has not been previously reported and (2) to study possible differences in the coexpression of p53 and tTG in various adrenal disorders. Using Northern blot analysis, p53 and tTG mRNAs were detected in each adrenal tissue examined including 5 normal human adrenals, 6 aldosterone-producing adenomas, 3 Cushing's adenomas, 1 primary nodular adrenocortical hyperplasia causing Cushing's syndrome in an infant, 12 non-hyperfunctioning adrenocortical adenomas, and 4 adrenocortical carcinomas. The results showed a significant positive correlation between these two mRNAs in all adrenal tissues except adrenocortical carcinomas. Compared to normal adrenals, high p53 mRNA levels were observed in aldosterone-producing and Cushing's adenomas and, most markedly, in a tissue from a primary nodular adrenocortical hyperplasia. Also, Cushing's adenomas had significantly higher tTG mRNA contents. Immunohistochemistry for wild-type and mutant p53 protein showed numerous p53 positive cells with a strong nuclear staining in a tissue from a primary nodular adrenocortical hyperplasia, whereas the p53 positive cells were absent, except those with a faint nuclear staining, in all other adrenal tissues. However, all adrenal tissues showed detectable p53 contents by the more sensitive method of luminometric immunoassay (LIA). Using this method, aldosterone-producing adenomas exhibited significantly higher p53 contents than normal adrenal tissues. These observations may support potentially important roles for p53 and tTG in adrenal pathophysiology, especially in mechanisms which influence the evolution and/or progression of aldosterone-producing and Cushing's adenomas and, most probably, hyperplasias.
研究了人正常和病理肾上腺组织中p53和组织转谷氨酰胺酶（tTG）基因的表达情况，目的有两个：（1）确定p53蛋白、其信使核糖核酸（mRNA），尤其是此前未报道过的tTG mRNA的组织含量；（2）研究p53和tTG在各种肾上腺疾病中共表达的可能差异。通过Northern印迹分析，在检测的每例肾上腺组织中均检测到了p53和tTG mRNA，包括5例正常肾上腺、6例醛固酮瘤、3例库欣腺瘤、1例导致婴儿库欣综合征的原发性结节性肾上腺皮质增生、12例无功能肾上腺皮质腺瘤和4例肾上腺皮质癌。结果显示，除肾上腺皮质癌外，所有肾上腺组织中这两种mRNA之间均存在显著正相关。与正常肾上腺相比，醛固酮瘤和库欣腺瘤中观察到较高的p53 mRNA水平，最显著的是在原发性结节性肾上腺皮质增生组织中。此外，库欣腺瘤的tTG mRNA含量显著更高。野生型和突变型p53蛋白的免疫组织化学显示，原发性结节性肾上腺皮质增生组织中有大量p53阳性细胞，核染色强，而在所有其他肾上腺组织中，除了核染色淡的细胞外，p53阳性细胞不存在。然而，通过更灵敏的发光免疫测定法（LIA），所有肾上腺组织均显示可检测到的p53含量。使用该方法，醛固酮瘤的p53含量显著高于正常肾上腺组织。这些观察结果可能支持p53和tTG在肾上腺病理生理学中的潜在重要作用，尤其是在影响醛固酮瘤和库欣腺瘤以及很可能还有增生的发生发展机制中。
