Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate

Aumüller, Gerhard; Holterhus, Paul Martin; Konrad, Lutz; Rahden, Bha von; Hiort, Olaf; Esquenet, Murielle; Verhoeven, Guido

doi:10.1007/s004290050131

Cited by 19 publications

(10 citation statements)

References 39 publications

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“…Xenograft staining was strong for both receptors 7 days post‐implantation, and increased at the 30‐day time‐point to reach a robust level of staining at 200 days. These findings accurately reflect previously published data indicating the strong presence of both androgen and estrogen receptors in stromal and epithelial cells of the developing human prostate .…”

Section: Discussionsupporting

confidence: 92%

Maturation of the developing human fetal prostate in a rodent xenograft model

et al. 2013

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Background Prostate cancer is the most commonly diagnosed non-skin cancer in men. The etiology of prostate cancer is unknown, although both animal and epidemiologic data suggest that early life exposures to various toxicants, may impact DNA methylation status during development, playing an important role. Methods We have developed a xenograft model to characterize the growth and differentiation of human fetal prostate implants (gestational age 12-24 weeks) that can provide new data on the potential role of early life stressors on prostate cancer. The expression of key immunohistochemical markers responsible for prostate maturation was evaluated, including p63, cytokeratin 18, α-smooth muscle actin, vimentin, caldesmon, Ki-67, prostate specific antigen, estrogen receptor-α, and androgen receptor. Xenografts were separated into epithelial and stromal compartments using laser capture microdissection (LCM), and the DNA methylation status was assessed in >480,000 CpG sites throughout the genome. Results Xenografts demonstrated growth and maturation throughout the 200 days of post-implantation evaluation. DNA methylation profiles of laser capture micro-dissected tissue demonstrated tissue-specific markers clustered by their location in either the epithelium or stroma of human prostate tissue. Differential methylated promoter region CpG-associated gene analysis revealed significantly more stromal than epithelial DNA methylation in the 30 and 90-day xenografts. Functional classification analysis identified CpG-related gene clusters in methylated epithelial and stromal human xenografts. Conclusion This study of human fetal prostate tissue establishes a xenograft model that demonstrates dynamic growth and maturation, allowing for future mechanistic studies of the developmental origins of later life proliferative prostate disease.

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Section: Discussionsupporting

confidence: 92%

Maturation of the developing human fetal prostate in a rodent xenograft model

et al. 2013

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“…1D). The androgen receptor protein has previously been shown to be expressed in both stromal as well as the epithelial cell types in prostate (26,27) and cellular localization of the unliganded receptor in transfected cell lines was predominantly cytoplasmic (28).…”

Section: The Morphology Of the Pubertal Prostate Is Distinct From Adumentioning

confidence: 99%

Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty

Dhanasekaran

Dash

et al. 2004

FASEB j.

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Testosterone production surges during puberty and orchestrates massive growth and reorganization of the prostate gland, and this glandular architecture is maintained thereafter throughout adulthood. Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCA) are common diseases in adulthood that do not develop in the absence of androgens. Our objective was to gain insight into gene expression changes of the prostate gland at puberty, a crucial juncture in prostate development that is androgen dependent. Understanding the role played by androgens in normal prostate development may provide greater insight into androgen involvement in prostatic diseases. Benign prostate tissues obtained from pubertal and adult age group cadaveric organ donors were harvested and profiled using 20,000 element cDNA microarrays. Statistical analysis of the microarray data identified 375 genes that were differentially expressed in pubertal prostates relative to adult prostates including genes such as Nkx3.1, TMEPAI, TGFBR3, FASN, ANKH, TGFBR2, FAAH, S100P, HoxB13, fibronectin, and TSC2 among others. Comparisons of pubertal and BPH expression profiles revealed a subset of genes that shared the expression pattern between the two groups. In addition, we observed that several genes from this list were previously demonstrated to be regulated by androgen and hence could also be potential in vivo targets of androgen action in the pubertal human prostate. Promoter searches revealed the presence of androgen response elements in a cohort of genes including tumor necrosis factor-alpha induced adipose related protein, which was found to be induced by androgen. In summary, this is the first report that provides a comprehensive view of the molecular events that occur during puberty in the human prostate and provides a cohort of genes that could be potential in vivo targets of androgenic action during puberty.

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“…For the detection of HA-tagged RBaK we used a monoclonal antibody directed against the viral HA epitope and directly labeled with horseradish peroxidase (HRP) from Roche. A rabbit polyclonal antibody raised against an amino-terminal peptide (aa 1-20) was used for the detection of the AR (Aumüller et al 1998) in combination with goat-anti-rabbit immunoglobins/ HRP from Dako as secondary antibody.…”

Section: Immunoprecipitationmentioning

confidence: 99%

The retinoblastoma protein-associated transcription repressor RBaK interacts with the androgen receptor and enhances its transcriptional activity

Hofman

Swinnen²,

Claessens³

et al. 2003

Journal of Molecular Endocrinology

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In search of potential androgen receptor coregulators we performed a yeast two-hybrid screening using the androgen receptor ligand-binding domain as bait and a human prostate cDNA library as prey and found that the carboxy-terminal domain of retinoblastoma-associated Krüppel protein (RbaK), a member of the Krüppel zinc finger protein family, interacts in a ligand-dependent way with the ligand-binding domain of the androgen receptor. RBaK was recently identified as a transcriptional regulator that interacts with the retinoblastoma protein and thereby influences E2F regulated transcription. The interaction of RBaK with the androgen receptor was further documented using mammalian two-hybrid experiments, in vitro binding studies and coimmunoprecipitation. Finally, we demonstrated that both RBaK and the retinoblastoma protein coactivate androgen receptor-mediated transcription in cotransfection experiments. In conclusion, our data show that RBaK interacts with the androgen receptor and increases its transcriptional activity. Moreover, the double interaction of RBaK with the retinoblastoma protein and with the androgen receptor provides a novel link between the androgen receptor and the regulation of the cell cycle.

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Immunohistochemistry and in situ hybridization of the androgen receptor in the developing human prostate

Cited by 19 publications

References 39 publications

Maturation of the developing human fetal prostate in a rodent xenograft model

Maturation of the developing human fetal prostate in a rodent xenograft model

Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty

The retinoblastoma protein-associated transcription repressor RBaK interacts with the androgen receptor and enhances its transcriptional activity

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