The expression and function of androgen receptor coactivator p44 and protein arginine methyltransferase 5 in the developing testis and testicular tumors.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Liang
John J
JJ
Department of Pathology, New York University School of Medicine, NY, USA.
Wang
Zhengxin
Z
Chiriboga
Luis
L
Greco
M Alba
MA
Shapiro
Ellen
E
Huang
Hongying
H
Yang
Ximing J
XJ
Huang
Jiaoti
J
Peng
Yi
Y
Melamed
Jonathan
J
Garabedian
Michael J
MJ
Lee
Peng
P
D000328:Adult; D000818:Animals; D015152:Blotting, Northern; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007984:Leydig Cell Tumor / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011496:Protein Methyltransferases / Q000235:genetics* / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases; D012333:RNA, Messenger / Q000235:genetics*; D018239:Seminoma / Q000378:metabolism / Q000473:pathology; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D014157:Transcription Factors; C478359:WDR77 protein, human; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases