WISP-2 as a Novel Estrogen-Responsive Gene in Human Breast Cancer Cells

Inadera, Hidekuni; Hashimoto, Shinichi; Dong, Hongyan; Suzuki, Takuji; Nagai, Shigenori; Yamashita, Taro; Toyoda, Nobuaki; Matsushima, Kouji

doi:10.1006/bbrc.2000.3276

Cited by 65 publications

(45 citation statements)

References 35 publications

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“…Subsequent data analysis showed that some genes were differentially modulated under each of our two experimental conditions, thereby indicating partial overlap between the two datasets. The VGID data sets included genes previously shown to be regulated in response to E 2 or TAM, such as Hsp27 (Porter et al 2001), pS2 (Inadera et al 2000), cathepsin D (Inadera et al 2000, Safe 2001), c-myc (Doisneau-Sixou et al 2003), ERK1 (Rabenoelina et al 2002) and -catenin (Gunin et al 2003), thereby substantiating the validity of our experimental approach. The fact that only immunophilin expression changes were not corroborated by microarray analyses may be explained by the observation that quantitative information obtained with small cDNA inserts as well as clones arising from less abundant mRNA species could be unreliable due to their propensity to generate weak signals falling within the 'noise' of microarray hybridization signals (Yang et al 1999).…”

Section: Discussionmentioning

confidence: 67%

Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells

Gadal¹,

Starzec²,

Bozic³

et al. 2005

Journal of Molecular Endocrinology

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To explore the mechanisms whereby estrogen and antiestrogen (tamoxifen (TAM)) can regulate breast cancer cell growth, we investigated gene expression changes in MCF7 cells treated with 17 -estradiol (E 2 ) and/or with 4-OH-TAM. The patterns of differential expression were determined by the ValiGen Gene IDentification (VGID) process, a subtractive hybridization approach combined with microarray validation screening. Their possible biologic consequences were evaluated by integrative data analysis. Over 1000 cDNA inserts were isolated and subsequently cloned, sequenced and analyzed against nucleotide and protein databases (NT/NR/EST) with BLAST software. We revealed that E 2 induced differential expression of 279 known and 28 unknown sequences, whereas TAM affected the expression of 286 known and 14 unknown sequences. Integrative data analysis singled out a set of 32 differentially expressed genes apparently involved in broad cellular mechanisms. The presence of E 2 modulated the expression patterns of 23 genes involved in anchors and junction remodeling; extracellular matrix (ECM) degradation; cell cycle progression, including G 1 /S check point and S-phase regulation; and synthesis of genotoxic metabolites. In tumor cells, these four mechanisms are associated with the acquisition of a motile and invasive phenotype. TAM partly reversed the E 2 -induced differential expression patterns and consequently restored most of the biologic functions deregulated by E 2 , except the mechanisms associated with cell cycle progression. Furthermore, we found that TAM affects the expression of nine additional genes associated with cytoskeletal remodeling, DNA repair, active estrogen receptor formation and growth factor synthesis, and mitogenic pathways. These modulatory effects of E 2 and TAM upon the gene expression patterns identified here could explain some of the mechanisms associated with the acquisition of a more aggressive phenotype by breast cancer cells, such as E 2 -independent growth and TAM resistance.

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Section: Discussionmentioning

confidence: 67%

Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells

Gadal¹,

Starzec²,

Bozic³

et al. 2005

Journal of Molecular Endocrinology

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“…Previous studies have demonstrated that the expression of human WISP-2/CCN5 is induced by serum and by oestrogens in the MCF-7 human breast cancer cells (Zoubine et al 2001, Inadera et al 2002, Banerjee et al 2003. Moreover, Inadera et al (2000) showed that the oestrogen-induced upregulation of human (h) WISP-2/CCN5 was abolished by actinomycin D but not by cycloheximide treatment indicating a direct transcriptional control by oestrogen receptor (ER). Furthermore, the upregulation of WISP-2/CCN5 under oestrogen treatment could be independent of DNA synthesis (Inadera 2003) although it has been demonstrated that hWISP-2 is important for proliferation in MCF-7 cells (Banerjee et al 2003(Banerjee et al , 2005.…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning and characterization of the human WISP-2/CCN5 gene promoter reveal its upregulation by oestrogens

Fritah¹,

Redeuilh²,

Sabbah³

2006

Journal of Endocrinology

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Wnt-1-induced signalling pathway protein-2 (WISP-2)/ connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN)5 is a member of the CCN family of growth factors and was identified as an oestrogen-inducible gene in the MCF-7 cell line. However, the role of WISP-2/ CCN5 in breast carcinogenesis remains unclear. In this study, we examined the mechanism by which oestrogens regulate the expression of human (h) Wnt-1 induced signalling pathway protein (WISP-2)/CCN5. Real-time RT-PCR showed that hWISP-2/CCN5 mRNA transcripts level is upregulated by oestrogens in the oestrogen receptor-positive human breast cancer cell lines MCF-7, T47D and ZR-75 . 1. Cloning of a 1 . 9 kb fragment of the hWISP-2/CCN5 5 0 -flanking sequence and subsequent analysis of potential transcription factor-binding sites identified a functional oestrogen response element site located between K581 and K569 upstream from the oestrogen-induced transcription start site. Transient transfections of MCF-7 cells with the cloned fragment showed that oestradiol caused an increase in reporter gene activity, which was inhibited by anti-oestrogens ICI 182 780 and 4-hydroxytamoxifen. Chromatin immunoprecipitation analysis revealed an oestradiol-dependent recruitment of the oestrogen receptor a to the oestrogen-responsive region of the hWISP-2/CCN5 gene promoter. We also showed that endogenous CREB-binding protein (CBP) and p21 WAF1/CIP1 are recruited to the chromosomal hWISP-2/CCN5 promoter in MCF-7 cells in an oestrogen-dependent manner, suggesting that CBP and p21 WAF1/CIP1 participate in the oestrogen receptor a-mediated transcriptional control of the hWISP-2/CCN5 gene.

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“…These observations are consistent with human studies demonstrating that WISP-2/CCN5 mRNA and protein expression are ''biphasic'' and markedly higher in noninvasive lesions compared with adjacent invasive tumor cells where expression levels are reduced and only sporadically detected (7). Furthermore, like other members of CCN family, including Cyr61 (10), WISP-2/CCN5 is a serum-and sex steroid (i.e., estrogen and progesterone) -inducible early responsive gene in human breast tumor cells (7,11,12). Silencing of WISP-2/CCN5 gene functions minimizes serum-induced breast tumor cell proliferation (7).…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Induces WISP-2/CCN5 Expression in Estrogen Receptor-α-Positive Breast Tumor Cells through Multiple Molecular Cross-talks

Banerjee

Sengupta²,

Saxena³

et al. 2005

Molecular Cancer Research

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Epidermal growth factor (EGF) is a mitogen for estrogen receptor (ER) -positive breast tumor cells, and it has been proven that EGF occasionally mimicked estrogen action and cross-talks with ER-A to exert its activity. Therefore, the present study was undertaken to explore whether EGF is able to modulate the expression of Wnt-1-induced signaling protein-2/connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed 5 (WISP-2/CCN5), an estrogenresponsive gene, in normal and transformed cell lines of the human breast and, if so, whether this induction is critical for EGF mitogenesis and what downstream signaling pathways are associated with this event. Here, we show that EGF-induced WISP-2 expression in ER-and EGF receptor -positive noninvasive MCF-7 breast tumor cells was dose and time dependent and that expression was modulated at transcription level. A synergism was seen in combination with estrogen. Moreover, small interfering RNA -mediated inhibition of WISP-2/CCN5 activity in MCF-7 cells resulted in abrogation of proliferation by EGF. The multiple molecular cross-talks, including the interactions between phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase signaling pathways and two diverse receptors (i.e., ER-A and EGFR), were essential in the event of EGF-induced WISP-2/CCN5 up-regulation in MCF-7 cells. Moreover, EGF action on WISP-2/CCN5 is restricted to ER-and EGFR-positive noninvasive breast tumor cells, and this

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WISP-2 as a Novel Estrogen-Responsive Gene in Human Breast Cancer Cells

Cited by 65 publications

References 35 publications

Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells

Integrative analysis of gene expression patterns predicts specific modulations of defined cell functions by estrogen and tamoxifen in MCF7 breast cancer cells

Molecular cloning and characterization of the human WISP-2/CCN5 gene promoter reveal its upregulation by oestrogens

Epidermal Growth Factor Induces WISP-2/CCN5 Expression in Estrogen Receptor-α-Positive Breast Tumor Cells through Multiple Molecular Cross-talks

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