9-cis-Retinoic Acid Inhibits Androgen Receptor Activity through Activation of Retinoid X Receptor

Chuang, Kuang Hsiang; Lee, Yi Fen; Lin, Wenxian; Chu, Chin Yi; Altuwaijri, Saleh; Wan, Yu‐Jui Yvonne; Chang, Chawnshang

doi:10.1210/me.2004-0181

Cited by 33 publications

(25 citation statements)

References 44 publications

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“…Beside the fact that Werner and DeLuca (2001) question the role of 9-cis RA as the physiological RXR ligand because the compound could not be identified in any tissue of analyzed rats, it has been shown for the fiddler crab Uca pugilator that a simultaneous expression and association of the RXR and the ecdysteroid receptor (EcR) is required to bind to responsive DNA elements (Durica et al 2002). Other receptors, including the AR, are also reported to form heterodimers with the RXR (Chuang et al 2005). According to these results, the AR and RXR affect their transcription mutually and it cannot be excluded that RXR activation might produce androgenic but also antiandrogenic effects by this mechanism.…”

Section: Neuropeptide Hypothesismentioning

confidence: 99%

Endocrine disruption in prosobranch molluscs: evidence and ecological relevance

et al. 2007

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Prosobranch snails represent almost 50% of all recent molluscs, are ubiquitously distributed, play important roles in various ecosystems and exhibit a variety of reproductive modes and life-cycle-strategies. Many of them attain life spans of several years, which in combination with their limited ability to metabolize organic chemicals, may contribute to the fact that prosobranchs constitute one of the most endangered taxonomic groups in aquatic ecosystems. Although it is not yet known to what extent endocrine disrupting chemicals (EDCs) contribute to this situation, the case of tributyltin (TBT) and its population-level impact on prosobranchs demonstrates the general susceptibility of these invertebrates. The existing evidence for comparable population-level effects in prosobranch snails by other androgens, antiandrogens, and estrogens is critically reviewed. The example of TBT demonstrates the difficulty to prove an endocrine mode of action for a given chemical. Although it is generally accepted that TBT causes imposex and intersex in prosobranch snails as a result of endocrine disruption, the detailed biochemical mechanism is still a matter of debate. The strengths and weaknesses of the five competing hypotheses are discussed, together with previously unpublished data. Finally, the ecological relevance of EDC effects on the population and community level and the application of prosobranchs for the assessment of EDCs are addressed.

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Section: Neuropeptide Hypothesismentioning

confidence: 99%

Endocrine disruption in prosobranch molluscs: evidence and ecological relevance

et al. 2007

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“…However, localization of AR to specific genomic sites is clearly more complex than simple sequence recognition. Similarly, AR can regulate transcription by distinct mechanisms; depending on cell or gene context, AR can activate or repress transcription, can functionally interact with other transcriptional regulators (Murtha et al 1997;Sato et al 1997) or with other intracellular receptors (Chen et al 1997;Lee et al 1999;Panet-Raymond et al 2000;Chuang et al 2005). Hormone response element (HRE) organization is likely a major determinant of receptor specificity and coregulator recruitment in a given chromosomal context (Lefstin and Yamamoto 1998).…”

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confidence: 99%

Cell- and gene-specific regulation of primary target genes by the androgen receptor

Bolton¹,

So²,

Chaivorapol³

et al. 2007

Genes Dev.

312

273

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The androgen receptor (AR) mediates the physiologic and pathophysiologic effects of androgens including sexual differentiation, prostate development, and cancer progression by binding to genomic androgen response elements (AREs), which influence transcription of AR target genes. The composition and context of AREs differ between genes, thus enabling AR to confer multiple regulatory functions within a single nucleus. We used expression profiling of an immortalized human prostate epithelial cell line to identify 205 androgen-responsive genes (ARGs), most of them novel. In addition, we performed chromatin immunoprecipitation to identify 524 AR binding regions and validated in reporter assays the ARE activities of several such regions. Interestingly, 67% of our AREs resided within ∼50 kb of the transcription start sites of 84% of our ARGs. Indeed, most ARGs were associated with two or more AREs, and ARGs were sometimes themselves linked in gene clusters containing up to 13 AREs and 12 ARGs. AREs appeared typically to be composite elements, containing AR binding sequences adjacent to binding motifs for other transcriptional regulators. Functionally, ARGs were commonly involved in prostate cell proliferation, communication, differentiation, and possibly cancer progression. Our results provide new insights into cell-and gene-specific mechanisms of transcriptional regulation of androgen-responsive gene networks.[Keywords: Androgen receptor (AR); androgen response element (ARE); transcription; steroid receptor; chromatin immunoprecipitation (ChIP); prostate cancer] Supplemental material is available at http://www.genesdev.org.

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“…7); however, 9-cis RA for RXR ligand significantly inhibited both p120α and p120β tranactivation induced by DHT. It should be noted that previous studies have shown that liganded RXR can function as a repressor to suppress the AR target gene [23]. The decreasing p120β function in the presence of 9-cis RA may be due to this direct proteinprotein interaction between RXR and AR.…”

Section: Expression Of P120α and β In Prostate Diseases And Cultured mentioning

confidence: 87%

A Novel Splice Variant of the Nuclear Coactivator p120 Functions Strongly for Androgen Receptor: Characteristic Expression in Prostate Disease

et al. 2008

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Abstract. We cloned a novel splicing variant for nuclear coactivator p120(α), designated as p120β and studied its function and expression in several human prostate diseases. Transfection assays demonstrated that p120β functions as a strong coactivator for androgen receptor (AR), but weakly for other nuclear receptors. GST-pull down assay showed that a glutamine-rich region of the p120 bound to the ligand-binding domain of AR. Interestingly, p120β mRNAs were expressed predominantly in the normal prostate, androgen-responsive prostate cancers and an androgen-sensitive prostate cancer cell line, LNCaP, but weakly in recurrent cancers and the androgen-insensitive prostate cancer cell lines PC3 and DU145. Furthermore, knockdown of p120α by siRNA abolished coactivator activity on thyroid hormone receptors (TR) and PPARγ, but did not affect that of ARs in PC3 cells. In addition, competitive assay with other nuclear receptors demonstrated that TR and PPARγ did not inhibit p120β-induced stimulation. These findings suggested that while p120α was essential for ligand-dependent stimulation of TRs and PPARγ, p120β acted as a coactivating protein predominantly for AR. PROSTATE cancer is the most common male malignancy in most Western countries, and the second leading cause of cancer death of men in the United States [1]. At the early stage of prostate cancer, the growth of prostate cancer cells is usually androgen-dependent and some tumor cells become androgen-independent in 6-18 months [2]. Androgen ablation through agonistic analogs of LHRH and antiandrogens, given either alone or in combination, can effectively treat prostate cancer [3]; however, hormone ablation therapy only causes temporary regression of prostate cancer. We have very few prognostic markers for prostate cancer recurrence because the molecular mechanism by which prostate cancer becomes androgen-independent is not clear. Therefore, the development of new diagnostic approaches to detect androgen-dependent or -independent tumor cells is important for improving the treatment and prediction of prognosis. Androgen receptor (AR) was the first factor highlighted as a cause of prostate cancer. Many investigations found mutation, amplification, overexpression, and a shorter CAG repeat sequence of the AR gene in androgen-independent prostate cancer [4][5][6][7][8]. The AR is a member of the steroid hormone superfamily of nuclear transcriptional factors. In the absence of ligand, AR is kept in a repressed state. In the presence of ligand, recruitment of coactivators such as SRC-1 [9]

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9-cis-Retinoic Acid Inhibits Androgen Receptor Activity through Activation of Retinoid X Receptor

Cited by 33 publications

References 44 publications

Endocrine disruption in prosobranch molluscs: evidence and ecological relevance

Endocrine disruption in prosobranch molluscs: evidence and ecological relevance

Cell- and gene-specific regulation of primary target genes by the androgen receptor

A Novel Splice Variant of the Nuclear Coactivator p120 Functions Strongly for Androgen Receptor: Characteristic Expression in Prostate Disease

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