Liang John J, Wang Zhengxin, Chiriboga Luis, Greco M Alba, Shapiro Ellen, Huang Hongying, Yang Ximing J, Huang Jiaoti, Peng Yi, Melamed Jonathan, Garabedian Michael J, Lee Peng
Department of Pathology, New York University School of Medicine, NY, USA.
J Urol. 2007 May;177(5):1918-22. doi: 10.1016/j.juro.2007.01.017.
The role of androgen receptor coactivators in testicular development and cancer formation is unclear. p44/Mep50 was identified as an androgen receptor coactivator that functions in a complex with protein arginine methyltransferase 5. We studied the expression of p44 and protein arginine methyltransferase 5 in developing fetal testis and adult testicular tumors, including seminomas and Leydig cell tumors.
A total of 30 human fetal testes from abortuses at a gestational age of 10 to 40 weeks, 33 human seminomas and 11 human Leydig cell tumors were retrieved from the archives of the departments of pathology. Immunohistochemistry was performed with affinity purified p44 and IgG purified protein arginine methyltransferase 5 polyclonal antibodies.
Protein arginine methyltransferase 5 and p44 were expressed predominantly as nuclear proteins in fetal Leydig cells and human adult nonneoplastic testes, including germ cells and Leydig cells, while they were expressed in the cytoplasm of germ cells of the fetal testis. Expression was strongest in the fetal testis during the second trimester. Compared to adult nonneoplastic testes, human seminoma and Leydig tumor cells showed a marked decrease in nuclear expression of p44 and protein arginine methyltransferase 5 with a concomitant marked increase in cytoplasmic expression of these proteins. Furthermore, average testicular size was increased by 29% in p44(+/-) heterzygotic mice.
These results suggest distinct functions of the nuclear and the p44/protein arginine methyltransferase 5 complexes in the developing fetal testis and in the oncogenesis of testicular tumors. Further studies are needed to confirm the functional relevance of these findings.
雄激素受体共激活因子在睾丸发育和癌症形成中的作用尚不清楚。p44/Mep50被鉴定为一种雄激素受体共激活因子，它与蛋白质精氨酸甲基转移酶5形成复合物发挥作用。我们研究了p44和蛋白质精氨酸甲基转移酶5在发育中的胎儿睾丸以及成人睾丸肿瘤（包括精原细胞瘤和Leydig细胞瘤）中的表达情况。
从病理科档案中获取了30例孕龄为10至40周流产胎儿的人胎儿睾丸、33例人精原细胞瘤和11例人Leydig细胞瘤。使用亲和纯化的p44和IgG纯化的蛋白质精氨酸甲基转移酶5多克隆抗体进行免疫组织化学检测。
蛋白质精氨酸甲基转移酶5和p44在胎儿Leydig细胞以及成人非肿瘤性睾丸（包括生殖细胞和Leydig细胞）中主要作为核蛋白表达，而在胎儿睾丸的生殖细胞胞质中表达。在妊娠中期胎儿睾丸中的表达最强。与成人非肿瘤性睾丸相比，人精原细胞瘤和Leydig肿瘤细胞中p44和蛋白质精氨酸甲基转移酶5的核表达明显降低，同时这些蛋白的胞质表达显著增加。此外，p44(+/-)杂合小鼠的平均睾丸大小增加了29%。
这些结果表明核内和p44/蛋白质精氨酸甲基转移酶5复合物在发育中的胎儿睾丸以及睾丸肿瘤的肿瘤发生过程中具有不同的功能。需要进一步研究来证实这些发现的功能相关性。
