Modulation of Androgen Receptor Transactivation by the SWI3-Related Gene Product (SRG3) in Multiple Ways

Hong, Chang Yee; Suh, Ji Ho; Kim, Kabsun; Gong, Eun-Yeung; Jeon, Sung Ho; Ko, Myunggon; Seong, Rho Hyun; Kwon, Ho; Lee, Keesook

doi:10.1128/mcb.25.12.4841-4852.2005

Cited by 28 publications

(19 citation statements)

References 55 publications

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“…This latter observation may have implications for AR, as BAF155 (and its murine homologue, SRG3) has been shown to regulate expression of specific SWI/SNF components, including BAF57, and is thought to serve as a critical regulator of SWI/SNF subunit levels (30,48). As would be expected, therefore, SRG3 is important for AR regulation (15).…”

Section: Discussionmentioning

confidence: 89%

“…SWI/SNF complexes alter nucleosome structure through the action of core ATPases (Brg1 or Brm), with specificity of SWI/SNF function rendered via the remaining 8 to 10 subunits, termed BRG1-associated factors (BAF). It has been previously reported that AR predominantly uses a subfamily of SWI/SNF complexes that depend on the Brm ATPase, but direct association of the receptor with SWI/SNF is likely fostered by direct interaction with the BAF57 or BAF155 subunits (13,15). Because the BAF57 subunit is not required for SWI/SNF ATPase activity (16), but is thought to direct specificity of the complex, it was hypothesized that this SWI/SNF subunit could be targeted for disruption in prostate cancer and therefore provide novel means of therapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

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Targeting the BAF57 SWI/SNF Subunit in Prostate Cancer: A Novel Platform to Control Androgen Receptor Activity

Link¹,

Balasubramaniam²,

Sharma³

et al. 2008

Cancer Research

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The androgen receptor (AR) is critical for disseminated prostate cancer proliferation and survival. AR activity is targeted either through prevention of ligand synthesis or through the use of antagonists that bind the COOH-terminal ligandbinding domain. Although initially effective, treatment fails due to restored AR activity in the presence of therapeutics. Thus, new means must be developed to target AR activity. The SWI/SNF chromatin remodeling complex is critical for AR transcriptional activity, and the BAF57 SWI/SNF subunit facilitates direct interaction with the receptor. Although selected SWI/SNF subunit expression is reduced in prostate cancer, we show that BAF57 is retained in human disease and is elevated in a subset of tumors. Functional analyses showed that BAF57 contributes uniquely to androgen-mediated stimulation of transcription without compromising the effectiveness of AR antagonists. Subsequent studies revealed that BAF57 is recruited to the AR DNA-binding domain/hinge region, which occurs concomitant with receptor activation. These data provided the basis for a novel inhibitor derived from BAF57 [BAF57 inhibitory peptide (BIPep)], which blocked AR residence on chromatin and resultant AR-dependent gene activation. Importantly, BIPep expression was sufficient to inhibit androgen-dependent prostate cancer cell proliferation in AR-positive cells. In summary, these data identify blockade of AR-BAF57 interaction as a novel means to target agonistinduced AR function in prostate cancer, and provide the first evidence that abrogation of SWI/SNF function can be developed as a point of therapeutic intervention in prostate cancer. [Cancer Res 2008;68(12):4551-8]

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Targeting the BAF57 SWI/SNF Subunit in Prostate Cancer: A Novel Platform to Control Androgen Receptor Activity

Link¹,

Balasubramaniam²,

Sharma³

et al. 2008

Cancer Research

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“…Although it has not been investigated, the loss of BRG1 and BRM could very well underlie the resistance to glucocorticoids in hematopoietic malignancies such as myeloma, lymphoma and leukemia, as well as in lung cancer (Choi et al, 2001b;Ko et al, 2004;Pottier et al, 2007). The estrogen receptor is also functionally linked to the SWI/SNF complex Belandia et al, 2002), and the androgen receptor is also SWI/SNF dependent (Inoue et al, 2002;Marshall et al, 2003;Hong et al, 2005;Link et al, 2005;Dai et al, 2008). We have found that BRG1 and BRM are lost in human prostate cancer samples, suggesting that a loss of SWI/SNF function may play a role in the development of hormone-refractory prostate cancer.…”

Section: Brm and Brg1 Control The Expression Of Genes That Are Involvmentioning

confidence: 99%

The SWI/SNF complex and cancer

2009

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The mammalian SWI/SNF complexes mediate ATPdependent chromatin remodeling processes that are critical for differentiation and proliferation. Not surprisingly, loss of SWI/SNF function has been associated with malignant transformation, and a substantial body of evidence indicates that several components of the SWI/SNF complexes function as tumor suppressors. This review summarizes the evidence that underlies this conclusion, with particular emphasis upon the two catalytic subunits of the SWI/SNF complexes, BRM, the mammalian ortholog of SWI2/SNF2 in yeast and brahma in Drosophila, and Brahma-related gene-1 (BRG1).

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“…Increasing evidence revealed the existence of a selffeedback regulation loop in steroid nuclear receptormediated signaling pathway (Zwijsen et al 1997, Shi et al 2001, Lauritsen et al 2002, Hong et al 2005. LRP16 is upregulated by estrogen in estrogen-sensitive epithelial cancer cells, and in turn, it enhances ERa-activated signaling transduction in a ligand-dependent manner by interacting with the receptor .…”

Section: Discussionmentioning

confidence: 99%

Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

Tian

Wu²,

Zhao³

et al. 2009

Journal of Endocrinology

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Previously, we investigated the induction effect of LRP16 expression by estrogen (17b-estradiol, E 2 ) and established a feed-forward mechanism that activated estrogen receptor a (ERa) transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ERa signaling transduction by functioning as an ERa coactivator. In this study, we demonstrated that LRP16 expression was upregulated in E 2 -responsive BG-1 ovarian cancer cells, but was downregulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The unliganded ERa upregulated LRP16 expression and enhanced LRP16 promoter activity in SKOV3 cells; however, this induction was blocked by estrogen stimulation. Results from chromatin immunoprecipitation experiment revealed a strong recruitment of the unliganded ERa at LRP16 promoter in the absence of estrogen; however, ERa was largely released from the DNA upon E 2 stimulation. Modulation in LRP16 expression level did not significantly change the proliferation rate of SKOV3 cells and the growth responsiveness of cells to E 2 . Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated estrogen response elementdependent ERa reporter gene activity and E 2 -induced c-Myc expression. Our study suggests a novel mechanism of estrogen resistance of ovarian cancer by which estrogenrepressed signaling pathway antagonizes estrogen-activated signaling transduction.

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Modulation of Androgen Receptor Transactivation by the SWI3-Related Gene Product (SRG3) in Multiple Ways

Cited by 28 publications

References 55 publications

Targeting the BAF57 SWI/SNF Subunit in Prostate Cancer: A Novel Platform to Control Androgen Receptor Activity

Targeting the BAF57 SWI/SNF Subunit in Prostate Cancer: A Novel Platform to Control Androgen Receptor Activity

The SWI/SNF complex and cancer

Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

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