Elevated levels of the steroidogenic factor 1 are associated with over-expression of CYP19 in an oestrogen-producing testicular Leydig cell tumour
| العنوان: | Elevated levels of the steroidogenic factor 1 are associated with over-expression of CYP19 in an oestrogen-producing testicular Leydig cell tumour |
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| المؤلفون: | Per Eystein Lønning, Hrvoje Miletic, Anne Hege Straume, Stian Knappskog, Kristian Løvås, Karsten Gravdal |
| المصدر: | European Journal of Endocrinology |
| بيانات النشر: | BioScientifica, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Steroidogenic factor 1, Adult, Male, medicine.medical_specialty, endocrine system, Endocrinology, Diabetes and Metabolism, Case Report, Leydig cell tumour, Steroidogenic Factor 1, Gene Expression Regulation, Enzymologic, Endocrinology, Aromatase, Testicular Neoplasms, Internal medicine, medicine, Biomarkers, Tumor, Humans, Regulation of gene expression, Leydig cell, biology, urogenital system, Liver receptor homolog-1, Promoter, Estrogens, General Medicine, medicine.disease, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Leydig Cell Tumor, biology.protein, Cancer research, hormones, hormone substitutes, and hormone antagonists |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1479-683X 0804-4643 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6419953e08930b6835725973a7978f27Test http://europepmc.org/articles/PMC3341656Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6419953e08930b6835725973a7978f27 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1479683X 08044643 |
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