Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals
| Autor: | Johannes C. Huber, Lukas A. Hefler, Reinhard Horvat, Alexander Reinthaller, Christian F. Singer, Dietmar Pils, Martin Bilban, Ulrike Kaufmann, Eva-Katrin Bentz, Clemens B. Tempfer |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty JUNB Administration Oral Gene Expression Transcription factor complex Breast Neoplasms Validation Studies as Topic Protein degradation Biology Injections Intramuscular Lynestrenol Internal medicine Gene expression Biomarkers Tumor medicine Humans Testosterone Breast Gonadal Steroid Hormones Gene Microarray analysis techniques Gene Expression Profiling Carcinoma Obstetrics and Gynecology Gene signature Microarray Analysis Gene expression profiling Chemotaxis Leukocyte Endocrinology Reproductive Medicine Sex Reassignment Procedures Cancer research Female Transsexualism Genes Neoplasm |
| Zdroj: | Fertility and Sterility. 94:2688-2696 |
| ISSN: | 0015-0282 |
| DOI: | 10.1016/j.fertnstert.2010.04.024 |
| Popis: | Objective To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT). Design Prospective cohort study. Setting Academic research institution. Patient(s) Five hormone-naive FtM transsexuals before and after HT. Intervention(s) Breast tissue biopsy before and after 2 years of intramuscular testosterone undecanoate (1,000 mg every 12 wk) and oral lynestrenole (5 mg daily), and gene signature analysis by global gene expression array covering 28,869 genes. Main Outcome Measure(s) Differential regulation of specific genes and gene expression signatures. Result(s) We identified 2,250 differentially expressed probe sets. One hundred twenty probe sets showed >2-fold change, of which 77 (64.2%) were up-regulated and 43 (35.8%) down-regulated. Genes involved in transcription were most overrepresented, with 43 out of 97 (44.3%) annotated probes, e.g., the transcription factor complex activator protein 1, including all three Jun genes (c-Jun, JunB, and JunD), two Fos genes (c-Fos and FosB), and activating transcription factor 3. In a Database for Annotation, Visualization, and Integrated Discovery analysis of the 2,007 down-regulated probe sets, proteins of the ribosome pathway and of two pathways involved in protein degradation, i.e., proteasome- and ubiquitin-mediated proteolysis, were significantly down-regulated. We identified eight breast cancer–associated gene expression signatures significantly overlapping with differentially regulated probe sets after cross-sex HT. Conclusion(s) Cross-sex HT in FtM transsexuals leads to the up-regulation and down-regulation of 243 and 2,007 distinct genes, respectively, and is associated with breast cancer–related gene expression signatures. |
| Databáze: | OpenAIRE |
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