Global Characterization of Transcriptional Impact of the SRC-3 Coregulator

Lanz, Rainer B.; Bulynko, Yaroslava; Malovannaya, Anna; Labhart, Paul; Wang, Liguo; Li, Wei; Qin, Jun; Harper, Mary‐Ellen; O’Malley, Bert W.

doi:10.1210/me.2009-0499

Cited by 56 publications

(52 citation statements)

References 68 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Forced overexpression of SRC-3 in mammary epithelial cells has been shown to be sufficient to promote mammary tumor formation, directly indicating it in breast cancer initiation (Lanz et al, 2010). Consistently, mice with SRC-3 deletion had suppressed oncogene-and carcinogen-induced breast cancer initiation, progression, and metastasis (Kuang et al, 2004;Yi et al, 2013).…”

Section: Introductionmentioning

confidence: 77%

Steroid Receptor Coactivator-3 Promotes Bladder Cancer Through Upregulation of CXCR4

Wang¹,

Liu²,

Qu³

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

The three homologous members of the p160 SRC family (SRC-1, SRC-2 and SRC-3) mediate the transcriptional functions of nuclear receptors and other transcription factors, and are the most studied of all the transcriptional co-activators. Recent work has indicated that the SRC-3 gene is subject to amplification and overexpression in various human cancers. Some of the molecular mechanisms responsible for SRC overexpression, along with the mechanisms by which SRC-3 promotes breast and prostate cancer cell proliferation and survival, have been identified. However, the function of SRC-3 in bladder cancer remains poorly understood. In the present study, our results indicate that overexpression of SRC-3 promotes bladder cancer cell proliferation whereas knockdown of SRC-3 results in inhibition. At the molecular level, we further established that CXCR4 is a transcriptional target of SRC-3. Therefore, our study first identified that SRC-3 plays a critical role in the bladder cancer, which may be a target beneficial for its prevention and treatment.

show abstract

Section: Introductionmentioning

confidence: 77%

Steroid Receptor Coactivator-3 Promotes Bladder Cancer Through Upregulation of CXCR4

Wang¹,

Liu²,

Qu³

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…Although recent genome-wide analysis of SRC-3 chromatin affinity sites in MCF-7 human breast cancer in response to estrogen induction did not identify the MIF gene, high-stringency HIF-binding site(s) near the MIF gene was identified in another recent genome-wide mapping [42,66]. It is reasonable that as a master transcriptional regulator, the ability of SRC-3 to regulate expression of its target genes is dependent on the transcriptional factors involved (i.e., HIF-1 vs ERα).…”

Section: Discussionmentioning

confidence: 99%

Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor

et al. 2012

Cell Res

View full text Add to dashboard Cite

SRC-3/AIB1 (steroid receptor coactivator 3/amplified in breast cancer 1) is an authentic oncogene that contributes to the development of drug resistance and poor disease-free survival in cancer patients. Autophagy is also an important cell death mechanism that has tumor suppressor function. In this study, we identified macrophage migration inhibitory factor (MIF) as a novel target gene of SRC-3 and demonstrated its importance in cell survival. Specifically, we showed that MIF is a strong suppressor of autophagic cell death. We further showed that suppression of MIF, in turn, induced autophagic cell death, enhanced chemosensitivity and inhibited tumorigenesis in a xenograft mouse tumorigenesis model. Our study demonstrated that regulation of MIF expression and suppression of autophagic cell death is a potent mechanism by which SRC-3 contributes to increased chemoresistance and tumorigenicity.

show abstract

“…The breast SNPs were previously shown to lie in two regulatory elements called PRE1 and PRE2 and regulate CCND1 [5]. The 3C results indicated that the PRE1/CCND1 interaction is breast specific, consistent with the extensive binding of the breast specific TFs ERα, SRC3 and FoxA1 at PRE1 [135,286]. The tissue specificity was also reflected in the luciferase results with PRE1 inducing a minimal change in CCND1 promoter activity when assayed in prostate cells (Figure 3.2E), whereas it exhibited high activity in breast cancer cell lines [5].…”

Section: Chapter 3 Page 78mentioning

confidence: 55%

“…A reduction in their expression as mediated by the risk SNPs is predicted to increase breast cancer susceptibility due to the vital role of DNA damage repair genes in the maintenance of genome stability [2]. Interrogation of publically available ChIP-seq datasets suggested that the putative lncRNAs arose from a bidirectional promoter that bound a number of transcription factors (TFs) relevant to breast cancer biology including the oestrogen receptor (ERα) [129], the pioneer factor FoxA1 [133], and the steroid receptor co-activator SRC3 [286] (Figure 4.4). H3K4me3 enrichment indicative of an active promoter is seen in MCF7 cells (Figure 4.4).…”

Section: Chapter 4 Page 88mentioning

confidence: 99%

See 1 more Smart Citation

The long range regulation of breast cancer associated genes

Betts¹

View full text Add to dashboard Cite

PrefacePage iBreast cancer is the most common non-cutaneous cancer of women and a major cause of mortality [1]. Genetic factors are the single biggest risk factor and 75% of the risk derives from common but low penetrance single nucleotide polymorphisms (SNPs) [2]. These are found using genome-wide association studies (GWAS) and the majority localize to non-coding regions of the genome [3] The identification of CCND1 as an interacting partner of PRE1 and PRE2 was done using a candidate gene approach with 3C (chromosome conformation capture) targeted confirmation of interaction. To detect other potential targets of PRE1 and PRE2 at the 11q13 locus using an agnostic approach, the 4Cseq and 5C techniques were used. These revealed a number of local interaction regions covering six gene promoters. A novel strategy using knockdown of enhancer RNA transcribed from PRE1 then identified the IGHMBP2 and CPT1A genes as likely additional targets of PRE1. Genome editing with transcription activator-like effector nucleases (TALENS) was also used, creating isogenic cell lines to clarify the effects of the SNPs in their native genomic context. Further functional work is required, however the range of techniques employed has substantially expanded our understanding of the 11q13 breast cancer risk locus and forms a template for future investigations of GWAS risk loci.To identify noncoding RNAs expressed at the 11q13 locus that may be interacting with PRE1 or PRE2 required the use of RNA Capture-seq. RNA Capture-seq involves a targeted enrichment step that greatly increases the sequencing depth at regions of interest and can reveal lowly expressed transcripts that may have not been found by traditional RNA-seq [7]. This identified one novel long non-coding RNA expressed from the (+) strand that was named CUPID1 and a second arising from the same locus on the (-) strand named CUPID2. They were located in the nucleus, oestrogen induced and both expressed relatively highly in ERα positive breast cancer cell lines but not in ERα The 11q13 locus is amplified in around 20% of breast cancers and is thought to contain a number of driver genes including CCND1 [8]. Given that CUPID1 and CUPID2 are widely over-expressed inERα positive breast cancer cell lines, it was hypothesized that they may also have a role in driving tumour growth. Publically available RNAseq data showed CUPID2 to be highly expressed in breast and renal cancer but not in normal tissue. Stable cell lines over-expressing the lncRNAs were then generated and subsequent oncogenic assays revealed that CUPID2 increased cellular proliferation and the efficiency of colony formation in breast cancer cells. A murine xenograft model confirmed these findings in vivo by demonstrating a marked increase in tumour size for the mice injected with cells over-expressing CUPID2. There is thus evidence that CUPID2 behaves as an oncogene and may be an additional driver of the 11q13 amplicon in ERα positive breast cancer.In summary, CPT1A and IGHMBP2 were identified as potential mediat...

show abstract

Global Characterization of Transcriptional Impact of the SRC-3 Coregulator

Cited by 56 publications

References 68 publications

Steroid Receptor Coactivator-3 Promotes Bladder Cancer Through Upregulation of CXCR4

Steroid Receptor Coactivator-3 Promotes Bladder Cancer Through Upregulation of CXCR4

Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor

The long range regulation of breast cancer associated genes

Contact Info

Product

Resources

About