Syreeta L. Tilghman

Publications (19) View all

• Source

  Available from: Matthew E Burow

  Article: Endocrine disruptor regulation of microRNA expression in breast carcinoma cells.

  Syreeta L Tilghman, Melyssa R Bratton, H Chris Segar, Elizabeth C Martin, Lyndsay V Rhodes, Meng Li, John A McLachlan, Thomas E Wiese, Kenneth P Nephew, Matthew E Burow
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  ABSTRACT: Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells. To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen. We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer.
  PLoS ONE 01/2012; 7(3):e32754. · 4.09 Impact Factor
• Article: Insulin-Like Growth Factor-1 Signaling Regulates miRNA Expression in MCF-7 Breast Cancer Cell Line.

  Elizabeth C Martin, Melyssa R Bratton, Yun Zhu, Lyndsay V Rhodes, Syreeta L Tilghman, Bridgette M Collins-Burow, Matthew E Burow
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  ABSTRACT: In breast carcinomas, increased levels of insulin-like growth factor 1 (IGF-1) can act as a mitogen to augment tumorigenesis through the regulation of MAPK and AKT signaling pathways. Signaling through these two pathways allows IGF-1 to employ mechanisms that favor proliferation and cellular survival. Here we demonstrate a subset of previously described tumor suppressor and oncogenic microRNAs (miRNAs) that are under the direct regulation of IGF-1 signaling. Additionally, we show that the selective inhibition of either the MAPK or AKT pathways prior to IGF-1 stimulation prevents the expression of previously described tumor suppressor miRNAs that are family and cluster specific. Here we have defined, for the first time, specific miRNAs under the direct regulation of IGF-1 signaling in the estrogen receptor positive MCF-7 breast cancer cell line and demonstrate kinase signaling as a modulator of expression for a small subset of microRNAs. Taken together, these data give new insights into mechanisms governing IGF-1 signaling in breast cancer.
  PLoS ONE 01/2012; 7(11):e49067. · 4.09 Impact Factor
• Source

  Available from: Lyndsay Rhodes

  Article: Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer.

  Lyndsay V Rhodes, Syreeta L Tilghman, Stephen M Boue, Shuchun Wang, Hafez Khalili, Shannon E Muir, Melyssa R Bratton, Qiang Zhang, Guangdi Wang, Matthew E Burow, Bridgette M Collins-Burow
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  ABSTRACT: The purpose of this study was to investigate the effects of glyceollins on the suppression of tumorigenesis in triple-negative breast carcinoma cell lines. We further explored the effects of glyceollins on microRNA and protein expression in MDA-MB-231 cells. Triple-negative (ER-, PgR- and Her2/neu-) breast carcinoma cells were used to test the effects of glyceollins on tumorigenesis in vivo. Following this procedure, unbiased microarray analysis of microRNA expression was performed. Additionally, we examined the changes in the proteome induced by glyceollins in the MDA-MB-231 cells. Tumorigenesis studies revealed a modest suppression of MDA-MB-231 and MDA-MB-468 cell tumor growth in vivo. In response to glyceollins we observed a distinct change in microRNA expression profiles and proteomes of the triple-negative breast carcinoma cell line, MDA-MB-231. Our results demonstrated that the glyceollins, previously described as anti-estrogenic agents, also exert antitumor activity in triple-negative breast carcinoma cell systems. This activity correlates with the glyceollin alteration of microRNA and proteomic expression profiles.
  Oncology letters 01/2012; 3(1):163-171. · 0.11 Impact Factor
• Article: Environmental signaling and reproduction: a comparative biological and chemical perspective.

  John A McLachlan, Syreeta L Tilghman, Matthew E Burow, Melyssa R Bratton
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  ABSTRACT: Reproduction is a critical element of life. Self-propagation in all living organisms ranging from bacteria to humans involves numerous common strategies. Underlying all reproductive strategies is the essential need for signaling molecules to initiate and maintain the process. In this paper we use comparative biological and chemical approaches to explore the origins and distribution of estrogen signaling as a pathway common to many life forms. In the process we illuminate the mechanisms whereby environmental agents alter reproduction and development. These mechanisms involve altered signaling pathways within cells and shifts in the targets of the signaling pathways to include regulators of gene transcription normally associated with other pathways. We also stress the role of signal cross talk in mediating hormone action.
  Molecular and Cellular Endocrinology 12/2011; 354(1-2):60-2. · 4.19 Impact Factor
• Article: Effects of SDF-1-CXCR4 signaling on microRNA expression and tumorigenesis in estrogen receptor-alpha (ER-α)-positive breast cancer cells.

  Lyndsay V Rhodes, Melyssa R Bratton, Yun Zhu, Syreeta L Tilghman, Shannon E Muir, Virgilio A Salvo, Chandra R Tate, Steven Elliott, Kenneth P Nephew, Bridgette M Collins-Burow, Matthew E Burow
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  ABSTRACT: The majority of breast cancer cases ultimately become unresponsive to endocrine therapies, and this progression of breast cancer from hormone-responsive to hormone-independent represents an area in need of further research. Additionally, hormone-independent carcinomas are characterized as being more aggressive and metastatic, key features of more advanced disease. Having previously shown the ability of the stromal-cell derived factor-1 (SDF-1)-CXCR4 signaling axis to promote primary tumorigenesis and hormone independence by overexpressing CXCR4 in MCF-7 cells, in this study we further examined the role of SDF-1/CXCR4 in the endogenously CXCR4-positive, estrogen receptor α (ER-α)-positive breast carcinoma cell line, MDA-MB-361. In addition to regulating estrogen-induced and hormone-independent tumor growth, CXCR4 signaling stimulated the epithelial-to-mesenchymal transition, evidenced by decreased CDH1 expression following SDF-1 treatment. Furthermore, inhibition of CXCR4 with the small molecule inhibitor AMD3100 induced CDH1 gene expression and inhibited CDH2 gene expression in MDA-MB-361 cells. Further, exogenous SDF-1 treatment induced ER-α-phosphorylation in both MDA-MB-361 and MCF-7-CXCR4 cells, demonstrating ligand-independent activation of ER-α through CXCR4 crosstalk. qPCR microRNA array analyses of the MDA-MB-361 and MCF-7-CXCR4 cell lines revealed changes in microRNA expression profiles induced by SDF-1, consistent with a more advanced disease phenotype and further supporting our hypothesis that the SDF-1/CXCR4 signaling axis drives ER-α-positive breast cancer cells to a hormone independent and more aggressive phenotype. In this first demonstration of SDF-1-CXCR4-induced microRNAs in breast cancer, we suggest that this signaling axis may promote tumorigenesis via microRNA regulation. These findings represent future potential therapeutic targets for the treatment of hormone-independent and endocrine-resistant breast cancer.
  Experimental Cell Research 08/2011; 317(18):2573-81. · 3.58 Impact Factor