Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals.
OBJECTIVE
To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT).


METHODS
Prospective cohort study.


METHODS
Academic research institution.


METHODS
Five hormone-naïve FtM transsexuals before and after HT.


METHODS
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.


METHODS
Differential regulation of specific genes and gene expression signatures.


RESULTS
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.


CONCLUSIONS
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.
Bentz
Eva-Katrin
EK
Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria.
Pils
Dietmar
D
Bilban
Martin
M
Kaufmann
Ulrike
U
Hefler
Lukas A
LA
Reinthaller
Alexander
A
Singer
Christian F
CF
Huber
Johannes C
JC
Horvat
Reinhard
R
Tempfer
Clemens B
CB
D000284:Administration, Oral; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001940:Breast / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D008234:Lynestrenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D046228:Microarray Analysis; D057829:Gender-Affirming Procedures; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014189:Transsexualism / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054928:Validation Studies as Topic
D014408:Biomarkers, Tumor; D012739:Gonadal Steroid Hormones; D013739:Testosterone; C010792:testosterone undecanoate; D008234:Lynestrenol