The p53/retinoblastoma-mediated repression of testicular orphan receptor-2 in the rhesus monkey with cryptorchidism.
Whereas the linkage of infertility to cryptorchidism, the failure of the testis to descend into the scrotum at birth, has been well documented, the detailed molecular mechanism remains unclear. Here we report that the testicular orphan receptor-2 (TR2) expression, which modulates many signal pathways, was completely repressed in the surgery-induced cryptorchidism of the rhesus monkey. Further studies link TR2 repression to the induction of p53 and results suggest that induced p53 could repress TR2 expression via the p53-->p21-->CDK-->Rb-->E2F signal pathway. In return, TR2 could also control the expression of p53 and Rb through the regulation of human papillomavirus 16 E6/E7 genes. Together, our data suggest a feedback control mechanism between TR2 and p53/Rb tumor suppressors, which might play important roles in male infertility associated with cryptorchidism.
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George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA.
Liu
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Collins
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Kim
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Chang
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D000818:Animals; D003456:Cryptorchidism / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000378:metabolism; D005246:Feedback; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007248:Infertility, Male / Q000209:etiology; D008253:Macaca mulatta; D008297:Male; D008954:Models, Biological; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger / Q000302:isolation & purification; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism* / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C068651:E6 protein, Human papillomavirus type 16; C539822:NR2C1 protein, human; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D018844:Cyclin-Dependent Kinases