Down-regulation of estrogen receptor beta and transcriptional coregulator SNURF/RNF4 in testicular germ cell cancer.
OBJECTIVE
The role of estrogens and androgens in the etiology and progression of testicular germ cell cancer is poorly understood. To gain insight into the role of sex steroid action in testicular tumorigenesis, we have measured mRNAs encoding estrogen receptor beta (ERbeta), androgen receptor (AR), and their coregulators SNURF/RNF4, PIASx, and PIAS1 in testicular germ cell tumors.


METHODS
We used real-time quantitative reverse transcription-PCR assay to compare the steroid receptor and coregulator mRNA levels in 12 matched samples of testicular tumors and adjacent normal tissues (seminomas n=8, nonseminomas n=4). In addition, ERbeta and SNURF/RNF4 protein immunoreactivity was analyzed from paraffin-embedded normal testis and tumor specimens.


RESULTS
ERbeta mRNA levels were down-regulated by 59% in seminomas (p=0.017), and those of AR and SNURF/RNF4 mRNAs were decreased by 75% and 67%, respectively, in seminomas and teratocarcinomas compared to paired normal samples (p=0.034 for both, Wilcoxon signed rank test), whereas the PIASx and PIAS1 mRNA were unaltered. ERbeta and SNURF/RNF4 were also clearly down-regulated at the protein level in testicular tumors.


CONCLUSIONS
Expression of ERbeta and SNURF/RNF4 was significantly lower in cancerous than in noncancerous testis tissue. Down-regulation of the ERbeta and the coregulator SNURF/RNF4 genes may play a role in testicular tumorigenesis.
Hirvonen-Santti
Sirpa J
SJ
Biomedicum Helsinki, Institute of Biomedicine, University of Helsinki, PO Box 63, FIN-00014 Helsinki, Finland.
Rannikko
Antti
A
Santti
Henrikki
H
Savolainen
Saija
S
Nyberg
Marcus
M
Jänne
Olli A
OA
Palvimo
Jorma J
JJ
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D015536:Down-Regulation; D047629:Estrogen Receptor beta; D018237:Germinoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013736:Testicular Neoplasms / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D014157:Transcription Factors