Abstract:
BACKGROUND AND OBJECTIVES:Testicular Leydig cell tumours (LCTs) are rare, steroid-secreting tumours. Elevated levels of aromatase (CYP19 or CYP19A1) mRNA have been previously described in LCTs; however, little is known about the mechanism(s) causing CYP19 over-expression. We report an LCT in a 29-year-old male with elevated plasma oestradiol caused by enhanced CYP19 transcription. DESIGN AND METHODS:First, we measured the intra-tumour expression of CYP19 and determined the use of CYP19 promoters by qPCR. Secondly, we explored CYP19 and promoter II (PII) for gene amplifications and activating mutations in PII by sequencing. Thirdly, we analysed intra-tumour expression of steroidogenic factor 1 (SF-1 (NR5A1)), liver receptor homologue-1 (LRH-1 (NR5A2)) and cyclooxygenase-2 (COX2 (PTGS2)). Finally, we analysed SF-1 for promoter mutations and gene amplifications. RESULTS:Similar to what has been recorded in normal Leydig cells, we first found the bulk of tumour CYP19 transcripts to be PII derived, excluding promoter shift as a cause of enhanced transcription. Secondly, we excluded CYP19 and PII gene amplifications, and activating mutations in PII, as causes of elevated CYP19 mRNA. We found SF-1 mRNA to be up-regulated in the tumour, while LRH-1 and COX2 were down-regulated. The finding of elevated SF-1 levels in the tumour was confirmed by immunohistochemistry. The elevated level of SF-1 was not due to promoter mutations or amplifications of the SF-1 gene. CONCLUSIONS:Our results strongly suggest that the elevated levels of SF-1 have induced PII-regulated CYP19 transcription in this tumour. These findings are of relevance to the understanding of CYP19 up-regulation in general, which may occur in several tissues, including breast cancer.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Straume AH,Løvås K,Miletic H,Gravdal K,Lønning PE,Knappskog Sdoi
10.1530/EJE-11-0849subject
Has Abstractpub_date
2012-05-01 00:00:00pages
941-9issue
5eissn
0804-4643issn
1479-683Xpii
EJE-11-0849journal_volume
166pub_type
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:European journal of endocrinology
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