Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis

Igarashi-Migitaka, Junko; Takeshita, Akira; Koibuchi, Noriyuki; Yamada, Shozo; Ohtani-Kaneko, Ritsuko; Hirata, Kazuaki

doi:10.1530/eje.1.01990

Cited by 12 publications

(7 citation statements)

References 50 publications

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“…Similarly, both AR mRNA and protein are found throughout the human tissue, with a declining concentration from the caput to the cauda epididymidis (Ezer and Robaire, 2002). Three p160 coactivators of the AR were immunolocalized in the rat epididymis; these type 1 coregulators exhibit cell type–specific expression in the tissue and differential localization within the cell, suggesting that they have specific roles in the epididymis (Igarashi‐Migitaka et al, 2005).…”

Section: Androgen Action: Androgens 5α‐reductases and The Armentioning

confidence: 99%

Androgen Action in the Epididymis

Robaire

Hamzeh

2011

Journal of Andrology

135

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Androgens are responsible for maintaining epididymal structure and functions. However, little is known about how androgen action is mediated and the mechanisms underlying the restoration of the integrity of epididymal cells after androgen deprivation. We first provide an overview of what is known about androgen action in this tissue and then present data on the initial and sequential roles of androgens in altering cellular architecture and function in an androgen-deprived condition. Using morphometric analysis and the rat model, we identified changes in epithelial cell height and lumen diameter, as well as in the numbers of proliferating cells in different regions and at various time points after androgen withdrawal and replacement. The sequence of gene activation or suppression that occurred in the androgen-deprived tissue was examined upon the readministration of the 2 active metabolites of testosterone, dihydrotestosterone (DHT) and estradiol. Although few genes were regulated by estradiol, many were affected by DHT. Epidermal growth factor (EGF) and insulinlike growth factor-1 (IGF1) appear to play an important role in the early response pathway activated by DHT because of their function in the regulation of the expression of many other genes. The intracellular signaling pathway involved in mediating the action of androgen in restoring epididymal epithelial cell integrity was investigated using the PC-1 epididymal cell line. IGF1 and EGF receptors were found to be important mediators of androgen receptor-mediated activation of the MAPK/ERK pathways. Together, these studies provide a greater understanding of the mechanisms of androgen action in the epididymis.

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Section: Androgen Action: Androgens 5α‐reductases and The Armentioning

confidence: 99%

Androgen Action in the Epididymis

Robaire

Hamzeh

2011

Journal of Andrology

135

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“…We, thus, examined the expression of these three p160 co-activators in LS174T cells by Western blot analysis. The specificity of monoclonal antibodies used in the present studies has been described elsewhere (Igarashi-Migitaka et al 2005). The Western blotting of cellular extracts of LS174T cells using each antibody detected a major band at 160 kDa (Fig.…”

Section: Resultsmentioning

confidence: 99%

The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells

Takeshita¹,

Inagaki²,

Igarashi-Migitaka³

et al. 2006

Journal of Endocrinology

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Resistance to anticancer drugs is often mediated by the overexpression of P-glycoprotein encoded by the multi-drug resistance (MDR1) gene. The nuclear receptor, steroid and xenobiotic receptor (SXR), is one of the key transcriptional regulators of MDR1 gene expression. A variety of xenobiotics bind to SXR, and stimulate transcription on xenobiotic-response elements (XREs), located in the MDR1 gene promoter. Diethylhexyl phthalate (DEHP) is widely used as a plasticizer for polyvinyl chloride (PVC) medical devices. Previous studies have shown that a significant amount of DEHP leaches from PVC infusion bags and lines during interventions, such as total parenteral nutrition, blood transfusion, and cancer chemotherapy. Thus, the leaching of DEHP during parenteral chemotherapy for cancer patients may facilitate MDR1 expression in various tissues, including cancer cells, which may promote drug resistance. To examine such a hypothesis, the effect of DEHP on SXR-mediated transcription of the MDR1 gene was studied in the human colon adenocarcinoma-derived cell line, LS174T cells, which endogenously express SXR. DEHP increased the SXR-mediated transcription of the MDR1 gene in luciferase-reporter assays. The induction by DEHP was abrogated when a reporter plasmid containing mutated DRC4 motif in the XRE was used. In a mammalian two-hybrid assay, DEHP recruited steroid receptor co-activator-1 to the ligand-binding domain of SXR. Finally, using real-time reverse transcriptase-PCR, we showed that DEHP increased MDR1 gene expression in a dose-dependent manner. We conclude that DEHP is an inducer of the MDR1 gene in this cell line. As such, the leaching of DEHP from the PVC medical devices may influence the MDR1 expression, which may induce resistance to drugs in certain populations of cancer cells.

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“…25 Animal models documented SRC-1 expression in Sertoli, Leydig, and germ cells of mice and rat testis. 27,28 On the basis our immunohistochemical studies, both SF-1 and SRC-1 are often expressed in ovarian stromal tumors including fibroma/fibrothecoma, and Sertoli cell tumors, and therefore, signet ring cell stromal tumor could be viewed as an ovarian sex-cord stromal tumor related to these tumors.…”

Section: Discussionmentioning

confidence: 98%

Oncogenic Activation of the Wnt/β-Catenin Signaling Pathway in Signet Ring Stromal Cell Tumor of the Ovary

Kopczyński

Kowalik²,

Chłopek³

et al. 2016

Applied Immunohistochemistry &Amp; Molecular Morphology

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Signet ring stromal cell tumor (SRSCT) of the ovary is a very rare benign ovarian neoplasm. To date, no underlying genetic mechanism has been identified. In this study, 50 oncogenes and tumor suppressor genes were evaluated for mutations in a typical SRSCT using the next-generation DNA sequencing approach. An in-frame deletion of 30 nucleotides in the glycogen serine kinase-3 beta phosphorylation region of the β-catenin gene (CTNNB1) was identified, and the finding was confirmed by Sanger sequencing. This deletion (c.68_97del) at the protein level would lead to a p.Ser23_Ser33delinsThr oncogenic-type mutation. Subsequent immunohistochemistry showed prominent nuclear accumulation of β-catenin and cyclin D1 in tumor cells. Thus, mutational activation of the Wnt/β-catenin pathway could be a crucial event in the molecular pathogenesis of SRSCT of the ovary. These findings may also assist in the diagnosis of this rare tumor.

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Differential expression of p160 steroid receptor coactivators in the rat testis and epididymis

Cited by 12 publications

References 50 publications

Androgen Action in the Epididymis

Androgen Action in the Epididymis

The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells

Oncogenic Activation of the Wnt/β-Catenin Signaling Pathway in Signet Ring Stromal Cell Tumor of the Ovary

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