Research Institute in Oncology and Hematology

Etienne Leygue

Breast Cancer

Dr Etienne Leygue PhD

Research Institute in Oncology and Hematology
5029 - 675 McDermot Ave
Winnipeg, MB R3E 0V9
phone:(204) 787-2785
Lab: (204) 787-2844
Fax: (204) 787-2190
Email: Dr Etienne Leygue PhD



My overall research focuses on the study of gene expression during human breast tumourigenesis and breast tumour progression. Designing therapies slowing down or inhibiting estrogen signaling in breast cells has already saved thousands of women. Unfortunately, resistance to a specific drug can occur in some patients and alternative treatments remain needed. It appears that a combination of drugs, targeting different critical points of estrogen signaling at different times, will provide a more efficient protection and overcome the potential resistance to a single drug.
The original face of the products of the SRA1 gene consisted of a non-coding functional RNA (SRA), able to activate estrogen receptors action. We have however demonstrated that this RNA also leads to the production of a protein (SRAP), which also acts as modulator of estrogen receptor action. We found that the action of this newly discovered SRAP is depending upon the receptor ligand, the cell context and the target genes considered.
The bi-faceted SRA RNA/SRAP system, consisting of a functional RNA and its corresponding protein, is therefore a newly discovered mechanism used by breast cells to modulate estrogen action. We hypothesize that characterization of SRA RNA/SRAP mechanism of action could provide new windows of opportunity to design innovative therapeutic or preventive strategies to fight breast cancer.

Team Members

  • Mohammad Hamedani (Technician)
  • Yi Yan (PhD)

Publications since 2010

PubMed Listed Publications
  1. Dynamic Histone Acetylation of H3K4me3 Nucleosome Regulates MCL1 Pre-mRNA Splicing. Khan DH, Gonzalez C, Tailor N, Hamedani MK, Leygue E., Davie JR. J Cell Physiol. 2016 Oct;231(10):2196-204. doi: 10.1002/jcp.25337. Epub 2016 Mar 6.
  2. Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1. Kotan LD, Cooper C, Darcan Ş, Carr IM, Özen S, Yan Y, Hamedani MK, G&uumlrb&uumlz F, Mengen E, Turan İ, Ulubay A, Akkuş G, Y&uumlksel B, Topaloğlu AK, Leygue E.. J Clin Res Pediatr Endocrinol. 2016 Jun 5;8(2):125-34. doi: 10.4274/jcrpe.3248. Epub 2016 Apr 18.
  3. The steroid receptor RNA activator protein (SRAP) controls cancer cell migration/motility. Yan Y, Cooper C, Hamedani MK, Guppy B, Xu W, Tsuyuki D, Zhang C, Nugent Z, Blanchard A, Davie JR, McManus K, Murphy LC, Myal Y, Leygue E.. FEBS Lett. 2015 Dec 21;589(24 Pt B):4010-8. doi: 10.1016/j.febslet.2015.11.007. Epub 2015 Nov 17.
  4. Claudin 1 in breast cancer. Zhou, B., Moodie, A., Blanchard, A., Leygue E.., Myal, Y., J. Clin.Med. 4 (12): 1960-1976, 2015
  5. The Steroid Receptor RNA protein (SRAP) controls cancer cell migration/motility. Yan, Y., Cooper, C., Hamedani, K.H., Guppy, B., Xu, W., Tsuyuki, D., Zhang, C., Nugent, Z., Blanchard, A., Davie, J.R., McManus, K., Murphy, L. C., Myal, Y., Leygue E.. Febs Let. S0014-5793(15)00978-3. doi: 10.1016/j.febslet.2015.11.007. [Epub ahead of print], 2015
  6. PDK2 Mediated Alternative Splicing Switches Bnip3 From Cell Death to Cell Survival. Gang, H., Dhingra, R., Lin, J., Hai, Y., Aviv, Y., Margulets, V., Hamedani, M., Thanasupawat, T., Leygue E.., Klonisch, T., Davie, J.R., Kirschenbaum, L.A. J Cell Biol. 210 (7): 1101-1115, 2015
  7. Claudin 1 Promotes Migration and Increases Sensitivity to Tamoxifen and Anticancer Drugs in Luminal-like Human Breast Cancer Cells MCF7. Zhou B, Blanchard A, Wang N, Ma X, Han J, Schroedter I, Leygue E, Myal Y. Cancer Invest. 2015 Aug 14:1-11
  8. Blanchard AA, Ezzati P, Shamshurin D, Nistor AC, Leygue E, Wilkins JA, Myal Y. Towards further defining the proteome of mouse saliva.Proteome Sci. 2015 Feb 25;13:10.
  9. Khan DH, Gonzalez C, Cooper C, Sun JM, Chen HY, Healy S, Xu W, Smith KT, Workman JL, Leygue E, Davie JR. RNA-dependent dynamic histone acetylation regulates MCL1 alternative splicing. Nucleic Acids Res. 2014 Feb;42(3):1656-70. doi: 10.1093/nar/gkt1134. Epub 2013 Nov 14.
  10. Yan Y, Penner CC, Skliris GP, Cooper C, Nugent Z, Blanchard A, Hamedani MK, Wang X, Myal Y, Murphy LC, Leygue E.. Steroid receptor RNA activator protein (SRAP) expression as a prognostic factor in ER+ human breast tumors.J Cancer Res Clin Oncol. 2013 Aug 2. [Epub ahead of print]
  11. Blanchard AA, Ma X, Dueck KJ, Penner C, Cooper SC, Mulhall D, Murphy LC, Leygue E., Myal Y. Claudin 1 expression in basal-like breast cancer is related to patient age. BMC Cancer. 2013 May 30;13:268. doi: 10.1186/1471-2407-13-268.
  12. Yan Y, Li X, Blanchard A, Bramwell VH, Pritchard KI, Tu D, Shepherd L, Myal Y, Penner C, Watson PH, Leygue E., Murphy LC. Expression of both Estrogen Receptor-beta 1 (ER- β 1) and its co-regulator Steroid Receptor RNA Activator Protein (SRAP) are predictive for benefit from tamoxifen therapy in patients with Estrogen Receptor-alpha (ER- α )-Negative Early Breast Cancer (EBC).Ann Oncol. 2013 Aug;24(8):1986-93. doi: 10.1093/annonc/mdt132. Epub 2013 Apr 11.
  13. Leygue E., Murphy LC. A bi-faceted role of estrogen receptor β in breast cancer. Endocr Relat Cancer. 2013 May 30;20(3):R127-39. doi: 10.1530/ERC-12-0389. Print 2013 Jun.
  14. Murphy LC, Leygue E.The role of estrogen receptor- β in breast cancer. Semin Reprod Med. 2012 Jan;30(1):5-13. Epub 2012 Jan 23. Review.
  15. Cooper C, Vincett D, Yan Y, Hamedani MK, Myal Y, Leygue E. Steroid receptor RNA activator bi-faceted genetic system: Heads or Tails? Biochimie. 2011 Nov;93(11):1973-80
  16. Gang H, Hai Y, Dhingra R, Gordon JW, Yurkova N, Aviv Y, Li H, Aguilar F, Marshall A, Leygue E, Kirshenbaum LA. A novel hypoxia-inducible spliced variant of mitochondrial death gene Bnip3 promotes survival of ventricular myocytes. Circ Res. 2011 Apr 29;108(9):1084-92.
  17. Myal Y, Leygue E, Blanchard AA. Claudin 1 in breast tumorigenesis: revelation of a possible novel "claudin high" subset of breast cancers. J Biomed Biotechnol. 2010;2010:956897.
  18. Chooniedass-Kothari S, Hamedani MK, Auge C, Wang X, Carascossa S, Yan Y, Cooper C, Vincett D, Myal Y, Jalaguier S, Cavailles V, Leygue E. The steroid receptor RNA activator protein is recruited to promoter regions and acts as a transcriptional repressor. FEBS Lett. 2010 Jun 3;584(11):2218-24.
  19. Chooniedass-Kothari S, Vincett D, Yan Y, Cooper C, Hamedani MK, Myal Y, Leygue E. The protein encoded by the functional steroid receptor RNA activator is a new modulator of ER alpha transcriptional activity. FEBS Lett. 2010 Mar 19;584(6):1174-80.

Funding

July 2016 - June 2018 PI: E. LEYGUE Title: Characterizing SRAP interactome using Proximity Biotinylation and Mass Spectrometry Type: CancerCare Manitoba Foundation operating grant Amount: $120,000 September 2013-August 2016 PI: E. LEYGUE Title: Estrogen receptor beta and SRA/SRAP system: functional interactions in triple negative breast cancer. Type: CBCF Operating Grant Amount: $374,938 Period: September 2012-August 2015 PI: J. DAVIE Co-PI: E. LEYGUE Title: Histone deacetylase inhibitors and alternative RNA splicing Type: CBCF Operating Grant Amount: $368,379

RIOH gratefully acknowledges the generous support of


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