• 한국어병학회지
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• 제16권2호
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• pp.111-118
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• 2003

Androgen plays an important role in the regulation of gonadotropin production in vertebrates . We have investigated the transcriptional pattern of androgen receptor (AR) in a variety of tissues in maturing male and female goldfish by RT-PCR. Specific primer for AR was designed based on goldfish AR gene from the GenBank (accession number AY090897). AR was shown 10 be maturity- and tissue-dependent gene expression pattern in goldfish. In immature male goldfish, significantly higher transcript level of AR was observed in the pituitary und testis , compared [0 brain and liver. Mature male goldfish showed a similar expression pattern to immature male goldfish. Interestingly. when compare to male goldfish, female goldfish showed AR mRNA expression that was found 10 be weak in pituitary, and very low expression in brain. They could not be found 10 have expression in any other tissues. Taken together. the- transcriptional analysis of AR depending on the tissue, sex. and maturity of a goldfish provides the opportunity for the study of goldfish reproductive physiology ,The results provided for the first time a comparison of the tissue distribution of AR mRNA in sexually maturating male and female goldfish.

• Genomics & Informatics
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• 제9권2호
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• pp.64-68
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• 2011

Monomelic amyotrophy (MA), also known as Hirayama disease, occurs mainly in young men and manifests as weakness and wasting of the muscles of the distal upper limbs. Here, we sought to identify a genetic basis for MA. Given the predominance of MA in males, we focused on candidate neurological disease genes located on the X chromosome, selecting two X-linked candidate genes, androgen receptor (AR ) and ubiquitin-like modifier activating enzyme 1 (UBA1). Screening for genetic variants using patients' genomic DNA revealed three known genetic variants in the coding region of the AR gene: one nonsynonymous single-nucleotide polymorphism (SNP; rs78686797) encoding Leu57Gln, and two variants of polymorphic trinucleotide repeat segments that encode polyglutamine (CAG repeat; rs5902610) and polyglycine (GGC repeat; rs3138869) tracts. Notably, the Leu57Gln polymorphism was found in two patients with MA from 24 MA patients, whereas no variants were found in 142 healthy male controls. However, the numbers of CAG and GGC repeats in the AR gene were within the normal range. These data suggest that the Leu57Gln polymorphism encoded by the X-linked AR gene may contribute to the development of MA.

• Molecules and Cells
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• 제28권5호
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• pp.495-499
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• 2009

Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.

• BMB Reports
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• 제53권12호
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• pp.634-639
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• 2020

In prostate cancer, the androgen receptor (AR) transcription factor is a major regulator of cell proliferation and metastasis. To identify new AR regulators, we focused on Mixed lineage leukemia 5 (MLL5), a histone-regulating enzyme, because significantly higher MLL5 expression was detected in prostate cancer tissues than in matching normal tissues. When we expressed shRNAs targeting MLL5 gene in prostate cancer cell line, the growth rate and AR activity were reduced compared to those in control cells, and migration ability of the knockdown cells was reduced significantly. To determine the molecular mechanisms of MLL5 on AR activity, we proved that AR physically interacted with MLL5 and other co-factors, including SET-1 and HCF-1, using an immunoprecipitation method. The chromatin immunoprecipitation analysis showed reduced binding of MLL5, co-factors, and AR enzymes to AR target gene promoters in MLL5 shRNA-expressing cells. Histone H3K4 methylation on the AR target gene promoters was reduced, and H3K9 methylation at the same site was increased in MLL5 knockdown cells. Finally, xenograft tumor formation revealed that reduction of MLL5 in prostate cancer cells retarded tumor growth. Our results thus demonstrate the important role of MLL5 as a new epigenetic regulator of AR in prostate cancer.

• Biomolecules & Therapeutics
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• 제31권2호
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• pp.210-218
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• 2023

Prostate cancer is the fifth leading cause of cancer-related mortality in men, primarily because of treatment resistance, recurrence, and metastasis. In the present study, we investigated the role of paracrine interleukin-8 (IL-8) in the antagonistic expression of IL-8 and androgen receptor (AR), and the contribution of IL-8 to prostate cancer aggressiveness. In hormone-responsive LNCaP cells that do not express IL-8, recombinant IL-8 treatment significantly increased expressions of IL-8, CXC chemokine receptor 2 (CXCR2), matrix metalloproteinase (MMP)-2/9, Snail, and vimentin. IL-8 treatment significantly decreased AR and E-cadherin expression. IL-8-induced gene expression changes were suppressed by navarixin, a CXCR1/2 inhibitor, and gallein, a Gβγ inhibitor. In PC-3 androgen-refractory prostate cancer cells, IL-8 knockdown reduced expressions of CXCR2, MMP-2/9, Snail, and vimentin, and increased AR and E-cadherin expressions at the mRNA and protein levels. Co-culture with MEG-01 human megakaryocytic cells secreting high levels of IL-8 induced gene expression changes in both LNCaP and PC-3 cells, similar to those induced by IL-8 treatment. The altered gene expressions were accompanied by significant activation of transcription factor Snail in LNCaP and PC-3 cells. Treatment with the CXCR blocker navarixin inhibited the invasion of PC-3 cells but not LNCaP cells. However, invasion induced by MEG-01 was inhibited by navarixin in both LNCaP and PC-3 cells. The collective findings demonstrate that IL-8 enhances CXCR2 expression, which antagonistically regulates AR expression. More importantly, through changes in IL-8/CXCR2-regulated gene expression, IL-8 induces antiandrogen therapy resistance and epithelial-mesenchymal transition in prostate cancer.

• Annals of Pediatric Endocrinology and Metabolism
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• 제23권4호
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• pp.220-225
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• 2018

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent $M{\ddot{u}}llerian$ duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4949-4954
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• 2015

The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and $ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and $ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.

• 대한화학회지
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• 제50권1호
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• pp.37-45
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• 2006

연구에서는 모세관 젤 전기 영동에서 분자체 역할을 하는 poly(ethylene oxide)를 이용하여 남성불임(Androgen receptor) 유전자의 정확한 CAG 반복 배열의 길이를 측정하였다. 표준물질인 X174 RF/Hae III, 100bp step ladder를 이용하여 non-linear regression analysis를 통한 81명의 한국의 불임 남성과 89명의 정상적인 한국 남성을 대조군으로 하여, 남성 불임과 관련된 AR gene의 exon 1의 CAG 반복 수를 측정하였다. 불임 남성의 CAG 반복 길이는 24.97±2.6 range, 17-29)이고, 정상인 남성은 23.99±2.4(range, 18-29)이다. P값은 0.018로써(<0.05) 두 그룹의 결과는 통계학적으로 주목 할 수 있는 차이를 나타내었다.

• 한국식품영양과학회지
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• 제42권10호
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• pp.1539-1543
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• 2013

본 연구에서는 Terminalia chebula Retz.의 성숙열매인 가자 메탄올 추출물(TCME)을 이용하여 HAT 활성을 억제함으로써 AR의 아세틸화 감소를 유도하여 전립선암세포의 성장을 억제하였다. TCME의 처리는 HAT 활성을 100 ${\mu}g/mL$의 농도에서 50% 이상 저해하였으며, p300과 CBP 등의 특이적 HAT 단백질에서도 유의적인 저해활성을 보였다. TCME를 0~100 ${\mu}g/mL$로 안드로젠 수용체 의존적 전립선 암세포인 LNCaP에 처리한 결과, reporter assay에서 AR 매개 전사를 억제하고 AR target gene의 mRNA 발현을 억제하였다. 동일 농도에서 AR의 아세틸화가 감소한 결과를 보였으며, 결국 전립선암세포주의 성장억제를 유도하였다. 이같은 결과에서 가자 메탄올 추출물은 HAT 활성을 억제하며, AR의 아세틸화를 감소시킴으로써 효과적인 전립선암 치료소재로 개발될 수 있는 가능성이 있음을 제안한다.

• Molecules and Cells
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• 제28권3호
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• pp.189-194
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• 2009

The modulating effect of IGF-I on the regulation of AR gene expression and activation in skeletal muscle cells remains poorly understood. In this study, the effects of IGF-I treatment on AR induction and activation in the absence of AR ligands were examined. Differentiating C2C12 cells were treated with different concentrations (0-250 ng/ml) of IGF-I or for various periods of time (0-60 min) of 250 ng/ml IGF-I. Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent increase in total AR and phosphorylated AR (Ser 213). IGF-I treatment also led to significantly increased AR mRNA expression when compared with the control. The levels of skeletal ${\alpha}-actin$ and myogenin mRNA, known target genes of AR, were also significantly upregulated after 5 or 10 min of treatment with IGF-I. Confocal images revealed that IGF-I stimulated nuclear localization of AR in the absence of ligands. In addition, an electrophoretic mobility shift assay indicated that IGF-I stimulated the AR DNA binding activity in a time-dependent manner. The present results suggest that IGF-I stimulates the expression and activation of AR by ligand-independent mechanism in differentiating C2C12 mouse skeletal muscle cells.