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"Building a Healthy Tomorrow"  TM

Laura Gillespie

BioMedical Sciences
B.Sc., Ph.D. Ottawa

Professor of Molecular Oncology

Terry Fox Cancer Research Laboratories
Division of BioMedical Sciences
Faculty of Medicine
Memorial University of Newfoundland
St. John’s, NL, Canada A1B 3V6
t: 709-864-6066 / 709-864-3334 / 709-864-3335

Role of MIER1α, a novel FGF response gene, in breast cancer

Polypeptide growth factors are known to have pleiotropic effects on cells, ranging from the stimulation of cell proliferation, the control of cell migration, cell survival and the regulation of cell differentiation. It has become apparent that many of the known oncogenes, i.e. those genes that when altered can contribute to cancerous transformation, are growth factors, their cellular receptors or components of their intracellular signaling pathways. Therefore, the elucidation of the regulatory mechanisms governing the cellular response to growth factors will further our understanding of how misregulation can lead to cancer.
Our research was focused on fibroblast growth factor (FGF) and one of the approaches we took was to isolate and characterize genes that are the initial nuclear targets of FGF signal transduction: the ‘immediate-early’ genes. Immediate-early genes are the most likely to function as “master” regulatory genes and characterization of such genes would not only enable us to determine their role in growth and differentiation, but will contribute to our understanding of diseases such as cancer. Our work has led to the discovery1 of several novel FGF response genes, including one called MIER1 that encodes a transcription/chromatin regulatory molecule2-4. Recently, we have characterized a novel isoform, MIER1α, that is specifically expressed in endocrine and endocrine response tissues5 and interacts with hormone-dependent nuclear receptors, in particular the estrogen receptors (ERs)6. Our analysis of breast tumour samples has demonstrated that MIER1α is a key negative regulator of the cellular response to estrogen and that it has the potential to play a critical role in the development and progression of breast cancer6.

Currently, the research in my lab is focused on elucidating the specific molecular mechanisms of ERα regulation by MIER1α and exploring its role in the development of invasive breast carcinoma.
This work is supported by research grants from the Canadian Institutes of Health Research and the Canadian Breast Cancer Foundation-Atlantic Chapter.

Selected Publications
1. Gillespie, L.L. and G.D. Paterno U.S. Patent No. 6746867, issued June 8, 2004.
2. Ding, Z., Gillespie, L. L. and G. D. Paterno 2003 Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of HDAC1 to their conserved ELM2 domain. Mol. Cell. Biol. 23: 250-258.
3. Ding, Z., Gillespie, L. L. and G. D. Paterno 2004 The SANT domain of hMI-ER1 interacts with Sp1 to interfere with GC box recognition and repress transcription. J. Biol. Chem. 279: 28009-28016.
4. Blackmore, T.M., Mercer, F.C., Paterno, G.D. and L.L. Gillespie 2008 The transcriptional cofactor MIER1-beta negatively regulates histone acetyltransferase activity of the CREB-binding protein. BMC Research Notes, 1, 68.
5. Thorne, L.B., McCarthy, P.L., Paterno, G.D. and L.L. Gillespie 2008 Protein expression of the transcriptional regulator MI-ER1 alpha in adult mouse tissues. J. Mol. Histol. 39, 15-24.
6. McCarthy, P.L., Mercer, F.C., Savicky, M.W.J., Carter, B.A. Paterno, G.D. and L.L. Gillespie 2008 Changes in subcellular localization of MI-ER1a, a novel estrogen receptor-a interacting protein, is associated with breast cancer progression. Br J Cancer, 99, 639-646.

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