Expression and regulation of Cyr61 in human breast cancer cell lines

Tsai, Miaw Sheue; Bogart, Daphne F.; Li, Patricia; Mehmi, Inderjit; Lupu, Ruth

doi:10.1038/sj.onc.1205131

Cited by 68 publications

(26 citation statements)

References 36 publications

(34 reference statements)

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“…Expression of cyr61 has been reported to be induced by estrogen in breast cancer cells [69,70] and human myometrial explants [70], which is consistent with the up-regulation of cyr61 expression in our study. Expression of bcl2 was down-regulated in our study, but previous reports have shown both induction and repression of bcl-2 expression by estrogen, potentially in a tissue specific manner [71-75].…”

Section: Discussionsupporting

confidence: 92%

Identification of Estrogen Target Genes during Zebrafish Embryonic Development through Transcriptomic Analysis

et al. 2013

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Estrogen signaling is important for vertebrate embryonic development. Here we have used zebrafish (Danio rerio) as a vertebrate model to analyze estrogen signaling during development. Zebrafish embryos were exposed to 1 µM 17β-estradiol (E2) or vehicle from 3 hours to 4 days post fertilization (dpf), harvested at 1, 2, 3 and 4 dpf, and subjected to RNA extraction for transcriptome analysis using microarrays. Differentially expressed genes by E2-treatment were analyzed with hierarchical clustering followed by biological process and tissue enrichment analysis. Markedly distinct sets of genes were up and down-regulated by E2 at the four different time points. Among these genes, only the well-known estrogenic marker vtg1 was co-regulated at all time points. Despite this, the biological functional categories targeted by E2 were relatively similar throughout zebrafish development. According to knowledge-based tissue enrichment, estrogen responsive genes were clustered mainly in the liver, pancreas and brain. This was in line with the developmental dynamics of estrogen-target tissues that were visualized using transgenic zebrafish containing estrogen responsive elements driving the expression of GFP (Tg(5xERE:GFP)). Finally, the identified embryonic estrogen-responsive genes were compared to already published estrogen-responsive genes identified in male adult zebrafish (Gene Expression Omnibus database). The expressions of a few genes were co-regulated by E2 in both embryonic and adult zebrafish. These could potentially be used as estrogenic biomarkers for exposure to estrogens or estrogenic endocrine disruptors in zebrafish. In conclusion, our data suggests that estrogen effects on early embryonic zebrafish development are stage- and tissue- specific.

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Section: Discussionsupporting

confidence: 92%

Identification of Estrogen Target Genes during Zebrafish Embryonic Development through Transcriptomic Analysis

et al. 2013

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“…A higher level of Cyr61 is found in breast cancer and it is shown to induce estrogen-independence and to promote invasiveness of breast cancer [32]. Cyr61 is shown to have elevated mRNA and protein levels in pancreatic cancer [33].…”

Section: Discussionmentioning

confidence: 99%

Cyr61/CCN1 Is Regulated by Wnt/β-Catenin Signaling and Plays an Important Role in the Progression of Hepatocellular Carcinoma

Ding

Sun

et al. 2012

PLoS ONE

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Abnormal activation of the canonical Wnt signaling pathway has been implicated in carcinogenesis. Transcription of Wnt target genes is regulated by nuclear β-catenin, whose over-expression is observed in Hepatocellular Carcinoma (HCC) tissue. Cyr61, a member of the CCN complex family of multifunctional proteins, is also found over-expressed in many types of tumor and plays dramatically different roles in tumorigenesis. In this study, we investigated the relationship between Cyr61 and β-catenin in HCC. We found that while Cyr61 protein was not expressed at a detectable level in the liver tissue of healthy individuals, its expression level was elevated in the HCC and HCC adjacent tissues and was markedly increased in cancer-adjacent hepatic cirrhosis tissue. Over-expression of Cyr61 was positively correlated with increased levels of β-catenin in human HCC samples. Activation of β-catenin signaling elevated the mRNA level of Cyr61 in HepG2 cells, while inhibition of β-catenin signaling reduced both mRNA and protein levels of Cyr61. We identified two TCF4-binding elements in the promoter region of human Cyr61 gene and demonstrated that β-catenin/TCF4 complex specifically bound to the Cyr61 promoter in vivo and directly regulated its promoter activity. Furthermore, we found that over-expression of Cyr61 in HepG2 cells promoted the progression of HCC xenografts in SCID mice. These findings indicate that Cyr61 is a direct target of β-catenin signaling in HCC and may play an important role in the progression of HCC.

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“…Expression of CYR61 mRNA is rapidly induced in an immediate early response manner by a spectrum of stimuli including growth factors, cytokines and estrogens [58-60]. We have demonstrated cyclical regulation of CYR61 in baboon endometrium, with maximal mRNA levels observed in shed menstrual endometrium [56].…”

Section: Angiogenic Profile Of Endometriotic Tissuesmentioning

confidence: 99%

A baboon model for endometriosis: implications for fertility

Hastings

Fazleabas

2006

Reprod Biol Endocrinol

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Endometriosis is one of the most common causes of chronic pelvic pain and infertility in women in the reproductive age group. Although the existence of this disease has been known for over 100 years our current knowledge of its pathogenesis and the pathophysiology of its related infertility remains unclear. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed a model of this disease in the non-human primate, the baboon (Papio anubis). Intraperitoneal inoculation of autologous menstrual endometrium results in the development of endometriotic lesions with gross morphological characteristics similar to those seen in the human. Multiple factors have been implicated in endometriosis-associated infertility. We have described aberrant levels of factors involved in multiple pathways important in the establishment of pregnancy, in the endometrium of baboons induced with endometriosis. Specifically, we have observed dysregulation of proteins involved in invasion, angiogenesis, methylation, cell growth, immunomodulation, and steroid hormone action. These data suggest that, in an induced model of endometriosis in the baboon, an increased angiogenic capacity, decreased apoptotic potential, progesterone resistance, estrogen hyper-responsiveness, and an inability to respond appropriately to embryonic signals contribute to the reduced fecundity associated with this disease.

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Expression and regulation of Cyr61 in human breast cancer cell lines

Cited by 68 publications

References 36 publications

Identification of Estrogen Target Genes during Zebrafish Embryonic Development through Transcriptomic Analysis

Identification of Estrogen Target Genes during Zebrafish Embryonic Development through Transcriptomic Analysis

Cyr61/CCN1 Is Regulated by Wnt/β-Catenin Signaling and Plays an Important Role in the Progression of Hepatocellular Carcinoma

A baboon model for endometriosis: implications for fertility

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