References of "Detry, Cédric"
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See detailGuide des Travaux Pratiques de Biologie
Peulen, Olivier ULg; Detry, Cédric ULg; Lamour, Virginie ULg et al

Learning material (2009)

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See detailCreb-1 and Ap-1 Transcription Factors Jund and Fra-2 Regulate Bone Sialoprotein Gene Expression in Human Breast Cancer Cells
Detry, Cédric ULg; Lamour, Virginie ULg; Castronovo, Vincenzo ULg et al

in BONE (2008), 42(2), 422-31

Bone sialoprotein (BSP) expression is detected in a variety of human osteotropic cancers. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone ... [more ▼]

Bone sialoprotein (BSP) expression is detected in a variety of human osteotropic cancers. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. In this study, we examined the transcriptional regulation of BSP gene expression in MDA-MB-231 and MCF-7 human breast cancer cells compared with Saos-2 human osteoblast-like cells. BSP human promoter deletion analyses delineated a -56/-84 region, which comprises a cAMP response element (CRE) that was sufficient for maximal promoter activity in breast cancer cell lines. We found that the basic fibroblast growth factor response element (FRE) also located in the proximal promoter was a crucial regulator of human BSP promoter activity in Saos-2 but not in breast cancer cells. Promoter activity experiments in combination with DNA mobility shift assays demonstrated that BSP promoter activity is under the control of the CRE element, through CREB-1, JunD and Fra-2 binding, in MDA-MB-231, MCF-7 and in Saos-2 cells. Forskolin, a protein kinase A pathway activator, failed to enhance BSP transcriptional activity suggesting that CRE site behaves as a constitutive rather than an inducible element in these cell lines. Over-expression of JunD and Fra-2 increased BSP promoter activity and upregulated endogenous BSP protein expression in MCF-7 and Saos-2 cells while siRNA-mediated inhibition of both factors expression significantly reduced BSP protein level in MDA-MB-231. Collectively, these data provide with new transcriptional mechanisms, implicating CREB and AP-1 factors, that control BSP gene expression in breast cancer cells. [less ▲]

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See detailRunx2-and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression
Lamour, Virginie ULg; Detry, Cédric ULg; Sanchez, Christelle ULg et al

in Journal of Biological Chemistry (2007), 282(50), 36240-36249

Bone sialoprotein (BSP) is a bone matrix glycoprotein whose expression coincides with terminal osteoblastic differentiation and the onset of mineralization. In this study we show that BSP expression is ... [more ▼]

Bone sialoprotein (BSP) is a bone matrix glycoprotein whose expression coincides with terminal osteoblastic differentiation and the onset of mineralization. In this study we show that BSP expression is considerably increased in confluent Saos-2 human osteosarcoma cells and in differentiating normal human osteoblasts, concomitantly with the decrease of Runx2, a key transcription factor controlling bone formation. Therefore, we investigated the role of Runx2 in the regulation of BSP expression in Saos-2 cells. Using a mobility shift assay, we demonstrated that Runx2 binds to the BSP promoter only in preconfluent cells. Histone deacetylase 3 (HDAC3) has been recently shown to act as a Runx2 co-repressor. Chromatin immunoprecipitation assays demonstrated that both Runx2 and HDAC3 are detectable at the BSP promoter in preconfluent Saos-2 cells but not when they are confluent and overexpress BSP. Consistently, nuclear Runx2 protein level is down-regulated, whereas Saos-2 cells became increasingly confluent. Finally, the suppression of HDAC3, Runx2, or both by RNA interference induced the expression of BSP at both mRNA and protein levels in Saos-2 cells. Our data demonstrate that Runx2 and HDAC3 repress BSP gene expression and that this repression is suspended upon osteoblastic cell differentiation. Both the nuclear disappearance of Runx2 and the non-recruitment of HDAC3 represent new means to relieve Runx2-mediated suppression of BSP expression, thus allowing the acquisition of a fully differentiated and mineralization-competent phenotype by osteoblast cells. [less ▲]

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See detailTranscriptome analysis reveals an osteoblast-like phenotype for human osteotropic breast cancer cells
Bellahcene, Akeila ULg; Bachelier, R.; Detry, Cédric ULg et al

in Breast Cancer Research and Treatment (2007), 101(2), 135-148

Metastatic breast cancer cells exhibit the selective ability to seed and grow in the skeleton. We and others have previously reported that human breast tumors which metastasize to the skeleton overexpress ... [more ▼]

Metastatic breast cancer cells exhibit the selective ability to seed and grow in the skeleton. We and others have previously reported that human breast tumors which metastasize to the skeleton overexpress bone matrix extracellular proteins. In an attempt to reveal the osteoblast-like phenotype of osteotropic breast cancer cells, we performed a microarray study on a model of breast cancer bone metastasis consisting of the MDA-MB-231 human cell line and its variant B02 selected for its high capacity to form bone metastases in vivo. Analysis of B02 cells transcriptional profile revealed that 11 and 9 out of the 50 most up- and down-regulated mRNAs, respectively, corresponded to genes which expression has been previously associated with osteoblastic differentiation process. Thus, osteoblast specific cadherin 11 which mediates the differentiation of mesenchymal cells into osteoblastic cells is up-regulated in B02. While S100A4, recently described as a key negative regulator of osteoblast differentiation, is the most down-regulated gene in B02 cells. RT-PCR and western blotting experiments allowed the validation of the modulation of several genes of interest. Using immunohistochemistry, performed on human breast primary tumors and their matched liver and bone metastases, we were able to confirm that the osteoblast-like pattern of gene expression observed in our model holds true in vivo. This is the first report demonstrating a gene-expression pattern corresponding to the acquisition of an osteomimetic phenotype by bone metastatic breast cancer cells. [less ▲]

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See detailExpression of dentin sialophosphoprotein in human prostate cancer and its correlation with tumor aggressiveness
Chaplet, Michael; Waltregny, David ULg; Detry, Cédric ULg et al

in International Journal of Cancer = Journal International du Cancer (2006), 118(4), 850-856

Recent studies have demonstrated that two SIBLING family members, bone sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate cancer. The expression of these proteins is associated ... [more ▼]

Recent studies have demonstrated that two SIBLING family members, bone sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate cancer. The expression of these proteins is associated with the acquisition of a metastatic phenotype by cancer cells and a poor prognosis for the patient. Dentin sialophosphoprotein (DSPP) shares several structural and genetic features with OPN and BSP. The presence of DSPP has been recently established in salivary glands, indicating that its expression is not restricted to mineralized tissues. However, its potential expression in human tumors has not been addressed yet. In this study, we sought to evaluate the expression of DSPP in human prostate cancer. Immunohistochemistry was performed on 69 prostate cancer specimens using LFMb-21 anti-DSPP monoclonal antibody. All of the prostate cancer lesions examined expressed detectable levels of DSPP, as compared with no or low level of expression in adjacent normal glands (p < 0.0001). High grade prostatic intraepithelial neoplasia (HGPIN) glands generally displayed DSPP expression levels that were similar to those found in neighboring cancer glands. DSPP expression was significantly associated with the pathological stage (p = 0.0087) and the Gleason score (p = 0.0176) of the tumors. Western Blot was performed on 5 representative prostate tumor extracts and 3 prostatic tumor cell lines (PC3, LNCaP and DU145). All tumor extracts and cell lines analyzed have been found to express DSPP. In addition, in situ hybridization was used to assess the presence of DSPP mRNA. DSPP was detected at the RNA level in both HGPIN and tumoral glands. This study shows for the first time that DSPP is ectopically expressed in human prostate cancer. The expression of this SIBLING protein strongly correlates with conventional histopathological prognostic indicators of prostate cancer progression. (c) 2005 Wiley-Liss, Inc. [less ▲]

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See detailDentin sialophosphoprotein expression correlates with progression markers in human prostate cancer
Chaplet, Michael; Waltregny, David ULg; Detry, Cédric ULg et al

in Journal of Bone and Mineral Research (2005), 20(Suppl. 2), 45

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See detailZoledronic acid up-regulates bone sialoprotein expression in osteoblastic cells through Rho GTPase inhibition
Chaplet, Michaël; Deroanne, Christophe ULg; Fisher, Larry W. et al

in Biochemical Journal (2004), 384(Pt 3), 591-598

Clinical practice reveals that osteoporotic women treated with BPs (bisphosphonates) show an increased bone mass density and a reduced risk of fractures. However, the mechanisms leading to these ... [more ▼]

Clinical practice reveals that osteoporotic women treated with BPs (bisphosphonates) show an increased bone mass density and a reduced risk of fractures. However, the mechanisms leading to these beneficial effects of BPs are still poorly understood. We hypothesized that ZOL (zoledronic acid), a potent third-generation BP, may induce the expression of proteins associated with the bone-forming potential of osteoblastic cells such as BSP (bone sialoprotein). Expression of BSP gene is up-regulated by hormones that promote bone formation and has been associated with de novo bone mineralization. Using real-time reverse transcriptase-PCR and Western-blot analysis, we demonstrated that ZOL increased BSP expression in Saos-2 osteoblast-like cells. Nuclear run-on and mRNA decay assays showed no effect at the transcriptional level but a stabilization of BSP transcripts in ZOL-treated cells. ZOL effect on BSP expression occurred through an interference with the mevalonate pathway since it was reversed by either mevalonate pathway intermediates or a Rho GTPase activator. We showed that ZOL impaired membrane localization of RhoA in Saos-2 cells indicating reduced prenylation of this protein. By the use of small interfering RNAs directed to RhoA and Rac1, we identified both Rho GTPases as negative regulators of BSP expression in Saos-2 cells. Our study demonstrates that ZOL induces BSP expression in osteoblast-like cells through inactivation of Rho GTPases and provides a potential mechanism to explain the favourable effects of ZOL treatment on bone mass and integrity. [less ▲]

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See detailFeeding of planktonic rotifers on ciliates: a method using natural ciliate assemblages labelled with fluorescent microparticles
Joaquim-Justo, Célia ULg; Detry, Cédric ULg; Caufman, F. et al

in Journal of Plankton Research (2004), 26(11), 1289-1299

A method was developed to allow direct measurements of predation exerted by metazooplankton on ciliates. The method relied on the use of ciliates labelled with fluorescent microparticles (FMP). Optimal ... [more ▼]

A method was developed to allow direct measurements of predation exerted by metazooplankton on ciliates. The method relied on the use of ciliates labelled with fluorescent microparticles (FMP). Optimal labelling conditions were determined with ciliates from cultures (Tetrahymena pyriformis) and with natural ciliate assemblages sampled in a river. Labelled T. pyriformis were used as tracer food to determine gut passage time (GPT) and ingestion rates of the rotifer Brachionus calyciflorus in the laboratory. Predation of metazooplankton from the lowland river Meuse (Belgium) was determined by labelling natural assemblages of ciliates and using them as tracer food for metazooplankters sampled in the river. Optimal labels of ciliates, i.e. sharp distribution of FMP in cells, were obtained with short incubations (10 min) and low FMP concentrations (1 x 10(5) mL(-1)). GPT varied between 30 and 45 min for B. calyciflorus and from 25 up to >35 min for rotifers from the river. The ingestion rate of B. calyciflorus fed with T. pyriformis was 3.3 +/- 0.6 ciliate rot(-1) h(-1), i.e. 1.4 +/- 0.3 ngC rot(-1) h(-1). Metazooplankton species for which the ingestion of ciliates could be measured were the rotifers Keratella cochlearis, Euchlanis dilatata and Synchaeta spp. Ingestion rates measured ranged from 0.4 to 12.5 ngC rot(-1) h(-1). The method proposed proved to be useful in estimating the predation of microplankton on ciliates in semi- in situ conditions; in further developments, labelled natural assemblages of ciliates could be used for in situ incubations with the Haney chamber. [less ▲]

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See detailDentin matrix protein 1 is expressed in human lung cancer
Chaplet, Michael; de Leval, Laurence ULg; Waltregny, David ULg et al

in Journal of Bone and Mineral Research (2003), 18(8), 1506-1512

We have previously shown that breast and prostate cancers express bone matrix proteins. DMPI expression was evaluated in 59 human lung cancer samples at the protein and mRNA levels. It was detectable in ... [more ▼]

We have previously shown that breast and prostate cancers express bone matrix proteins. DMPI expression was evaluated in 59 human lung cancer samples at the protein and mRNA levels. It was detectable in 80% of the cases, suggesting a potential role for DMP1 in tumor progression and bone metastasis. Introduction: Previously, we and others have shown that bone extracellular matrix proteins such as bone sialoprotein (BSP) and osteopontin (OPN) are expressed in various types of cancer that are characterized by a high affinity for bone including breast, prostate, and lung adenocarcinoma. Based on biochemical and genetic features, BSP, OPN, dentin matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP) have been recently classified in a unique family named SIBLING (small integrin-binding ligand, N-linked glycoprotein). Therefore, we investigated whether DMPI could also be detected in osteotropic cancers. Materials and Methods: We first used a cancer array for evaluating the relative abundance of DMP1 transcript in a broad spectrum of human cancer tissues. This screening showed that DMP1 was strongly detectable in lung tumors compared with normal corresponding tissue. In a second step, we used an immunophosphatase technique and a specific polyclonal antibody directed against DMPI to examine the expression of DMP1 in 59 human non-small cell lung cancer samples, including 29 squamous carcinoma, 20 adenocarcinoma, and 10 bronchioloalveolar carcinoma. Student's t-test was used to determine the statistical significance of immunostaining scores between the lung cancer histological groups studied and between cancer and normal lung tissues. Results: Our results show that DMP1 is detectable in 90% of the adenocarcinoma and squamous carcinoma analyzed while 8 of 10 bronchioloalveolar specimens were negative. DMP1 immunostaining intensity and extent scores were significantly higher in adenocarcinoma (p = 0.0004) and squamous carcinoma (p < 0.0001) samples compared with adjacent normal lung tissue. In situ hybridization experiments confirmed that DMP1 mRNA is localized in lung cancer cells. Conclusion: In this study, we show that a third SIBLING protein is ectopically expressed in lung cancer. The role of DMPI in lung cancer is largely unknown. Further studies are required to determine the implication of this protein, next to its sisters SIBLING proteins, in tumor progression and bone metastasis development. [less ▲]

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See detailDetection of bone sialoprotein in human (pre)neoplastic lesions of the uterine cervix
Detry, Cédric ULg; Waltregny, David ULg; Quatresooz, Pascale ULg et al

in Calcified Tissue International (2003), 73(1), 9-14

Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in the mineral compartment of developing bones. BSP is detected in a variety of human cancers, particularly those that metastasize to the ... [more ▼]

Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in the mineral compartment of developing bones. BSP is detected in a variety of human cancers, particularly those that metastasize to the skeleton. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. Since squamous cell carcinoma (SCCs) of the uterine cervix also frequently metastasizes to bone, we investigated whether BSP is expressed in human cervical cancer. We examined BSP expression in cervical tissue samples from 47 patients, including 19 normal tissues, 20 squamous intraepithelial lesions (SILs) (9 low and 11 high grade) and 8 invasive SCCs. BSP protein expression was evaluated by the immunophosphatase technique using a BSP polyclonal antibody in paraffin-embedded cervical biopsies. The abundance of BSP protein was significantly higher in invasive SCCs and high grade SILs than in normal cervix tissue samples and low grade SILs, which showed no or a low level of anti-BSP immunoreactivity. In situ hybridization experiments performed on representative cervix invasive SCCs frozen sections revealed that BSP transcripts were detectable in these lesions. Our study demonstrates that BSP expression is a common feature in high grade SILs and invasive SCCs of the uterine cervix. The prognostic value of BSP detection in these lesions and the potential role of BSP as an angiogenic factor in this type of cancer are currently under investigation. [less ▲]

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See detailUSE OF FLUORESCENTLY LABELLED PROTOZOANS TO INVESTIGATE THE PREDATION OF ROTIFERS ON PROTOZOOPLANKTON
Joaquim-Justo, Célia ULg; Detry, Cédric ULg; Thomé, Jean-Pierre ULg

Conference (2000, January 16)

The importance of trophic relationships between rotifers and protozoans in rivers are not yet well known, but as some authors have shown during the last decade, the predation exerted by rotifers on these ... [more ▼]

The importance of trophic relationships between rotifers and protozoans in rivers are not yet well known, but as some authors have shown during the last decade, the predation exerted by rotifers on these organisms might be of importance in the transfer of energy from the pico- and nanoplankton to the metazooplankton. Fluorescent polycarbonate beads of 0.45 µm in diameter were used to label the ciliate Tetrahymena pyriformis. Different combinations of labelling times and concentrations of microspheres were tested to achieve an optimal labelling of the ciliates (i.e. a maximal proportion of individuals having ingested the same number of microspheres). Live labelled Tetrahymena pyriformis were used to determine both the gut passage time and the ingestion rate of the rotifer Brachionus calyciflorus. The ingestion rates measured with relatively high densities of ciliates (from 30 to 500 cells.ml-1) were on average of 30 cells.ind-1.day-1. The ingestion rates yielded by this method were compared with ingestion rates measured by assessing the disappearance of the ciliates in experimental media during 5-6 hour incubations. Results from both methods were comparable but the use of fluorescently labelled prey items produced less variable results. [less ▲]

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