2 research outputs found
Activin is produced by rat Sertoli cells in vitro and can act as an autocrine regulator of Sertoli cell function
Regulation of androgen receptor (AR) mRNA expression was studied in
Sertoli cells and peritubular myoid cells isolated from immature rat
testis, and in the lymph node carcinoma cell line derived from a human
prostate (LNCaP). Addition of dibutyryl-cyclic AMP (dbcAMP) to Sertoli
cell cultures resulted in a rapid transient decrease in AR mRNA expression
(5 h), which was followed by a gradual increase in AR mRNA expression
(24-72 h). This effect of dbcAMP mimicked follicle-stimulating hormone
(FSH) action. In peritubular myoid cells, there was only a moderate but
prolonged decrease during incubation in the presence of dbcAMP, and in
LNCaP cells no effect of dbcAMP on AR mRNA expression was observed. When
Sertoli cells or peritubular myoid cells were cultured in the presence of
androgens, AR mRNA expression in these cell types did not change. This is
in contrast to LNCaP cells, that showed a marked reduction of AR mRNA
expression during androgen treatment. In the present experiments,
transcriptional regulation of AR gene expression in Sertoli cells and
LNCaP cells was also examined. Freshly isolated Sertoli cell clusters were
transfected with a series of luciferase reporter gene constructs, driven
by the AR promoter. It was found that addition of dbcAMP to the
transfected Sertoli cells resulted in a small but consistent increase in
reporter gene expression (which was interpreted as resulting from AR
promoter activity); a construct that only contained the AR 5' untranslated
region of the cDNA sequence did not show such a regulation. The same
constructs, transfected into LNCaP cells, did not show any transcriptional
down-regulation when the synthetic androgen R1881 was added to the cell
cultures. A nuclear transcription elongation experiment (run-on), however,
demonstrated that androgen-induced AR mRNA down-regulation in LNCaP cells
resulted from an inhibition of AR gene transcription. The present results
indicate that in Sertoli cells and LNCaP cells, hormonal effects on AR
gene transcription play a role in regulation of AR expression. However, AR
gene transcription in these cells is differentially regulated
Loss of Y-Chromosome during Male Breast Carcinogenesis
Loss of Y-chromosome (LOY) is associated with increased cancer mortality in males.
The prevalence of LOY in male breast cancer (BC) is unknown. The aim of this study is to assess the
presence and prognostic effect of LOY during male BC progression. We included male BC patients
diagnosed between 1989 and 2009 (n = 796). A tissue microarray (TMA) was constructed to perform
immunohistochemistry and fluorescent in situ hybridization (FISH), using an X and Y probe. We
also performed this FISH on a selected number of patients using whole tissue slides to study LOY
during progression from ductal carcinoma in situ (DCIS) to invasive BC. In total, LOY was present in
12.7% (n = 92) of cases, whereby LOY was associated with ER and PR negative tumors (p = 0.017 and
p = 0.01). LOY was not associated with the outcome. Using whole slides including invasive BC and
adjacent DCIS (n = 22), we detected a concordant LOY status between both components in 17 patients.
In conclusion, LOY is an early event in male breast carcinogenesis, which generally starts at the DCIS
stage and is associated with ER and PR negative tumor