National Center of Competence in Research - NCCR Molecular Oncology

Prof. Cathrin Brisken

Assistant Professor Tenure-Track

Prof. Cathrin Brisken received her MD in 1992 and a Doctorate in Medicine in 1993 at the Georg August University of Göttingen, Germany. She carried out postdoctoral work with Dr. R.A. Weinberg at the Whitehead Institute of Biomedical Research in Cambridge, MA, USA and became a research scientist there in 1999. In 2001 she was appointed assistant professor at the Cancer Center of the Massachusetts General Hospital, Harvard Medical School, Boston. In 2002, she joined ISREC as an associate scientist in the NCCR Molecular Oncology program and was nominated EPFL assistant professor (tenure-track) in September 2005. She is member of IBCSG (International Breast Cancer Study Group) Biological Protocol Working Group.

ISREC, School of Life Sciences
Ecole Polytechnique Fédérale (EPFL)

Cell fate determination - Genetic dissection of signaling pathways important in breast development and breast cancer

Breast cancer affects one of eight women in Switzerland, and is a leading cause of cancer-associated death worldwide. Clinically and biologically, breast cancer is an extremely heterogeneous disease that is closely linked to hormones. Breast cancer risk is affected by a woman’s lifetime hormone exposure; early pregnancies provide a protective effect and breast cancer risk increases with early menarche and late menopause both of which result in an increased number of menstrual cycles during a woman’s lifetime. Furthermore, hormones control the microenvironment of breast carcinomas and can thereby determine the course of the disease.

Hormones

The hormones act on a subset of cells in the milk ducts that possess specific receptors to detect them. These “sensor” cells translate the systemic needs communicated by the hormone concentrations and fluctuations into powerful local stimuli that change the behavior of many different cell types in the breast and activate progenitor cells. Physiologically, these processes are most important to coordinate growth and function of the mammary gland with reproductive requirements. During the development of breast cancer, tumor cells hijack them. Understanding the signaling mechanisms will help to identify novel approaches for preventing tumor progression.

List of publications

Cicalese, A.; Bonizzi, G.; Pasi C. E.; Faretta, M.; Ronzoni, S.; Giulini, B.; Brisken, C.; Minucci, S.; Di Fiore, P. P.; Pelicci, P. G. The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 18; 138(6): 1083-95 (2009)

Barbaroux, J.B., Beleut, M., Brisken, C., Mueller, C., Groves, R.W. Epidermal Receptor Activator of NF-kB Ligand Controls Langerhans Cells Numbers and Proliferation Langerhans cells numbers and proliferation. J Immunol. 181(2): 1103-8 (2008)

Mani, S. A., Guo, W., Liao, M.J., Ng. Eaton, E., Ayyanan, A., Zhou, A., Brooks, M., Reinhard, F., Zhang, C.C., Shipitsin, M., Campbell, L. l., Polyak, K., Brisken, C., Yang, J., Weinberg, R. A. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133(4): 704-15 (2008)

Boulay, A., Breuleux, M., Stephan, C., Fux, C., Brisken, C., Fiche, M., Wartmann, M., Stumm, M., Lane, H. A., Hynes, N.E. The Ret Receptor Tyrosine Kinase Pathway Functionally Interacts with the ERα Pathway in Breast Cancer. Cancer Res. 68(10): 3743-51 (2008)

Ciarloni, L., Mallepell, S., Brisken, C. Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development. Proc. Natl. Acad. Sci. U S A. 104(13):5455-60 (2007)

Ayyanan, A., Civenni, G., Morel, C., Ciarloni, L., Lefort, K., Mandinova, A., Raffoul, W., Fiche, M., Dotto, G.P., Brisken, C. Increased Wnt signaling triggers oncogenic conversion of human mammary cells by a Notch-dependent mechanism, Proc. Natl. Acad. Sci. USA, 103(10):3799-804 (2006)

Mallepell, S., Krust, A., Chambon, P., Brisken, C. Paracrine signaling through the epithelial Estrogen Receptor α is required for proliferation and morphogenesis in the mammary gland, Proc. Natl. Acad. Sci. USA, 103(7):2196-201 (2006)

Devgan, V., Mammucari, C., Millar, SE, Brisken, C, and Dotto, G. P. 21^WAF1/Cip1 is a negative transcriptional regulator of Wnt4 expression downstream of Notch1 activation. Genes and Development, 19:1485-95 (2005)

Farmer, P., Bonnefoi, H., Becette, V., Tubiana-Hulin, M., Fumoleau, P., Larsimont, D., MacGrogan, G., Bergh, J., Cameron, D., Goldstein, D., Duss, S., Nicoulaz, A-L., Fiche, M., Brisken, C, Delorenzi, M., and Iggo, R. Identification of molecular apocrine breast tumors by microarray analysis. Oncogene, 24, 4660-4671 (2005)

Pierre F, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz AL, Brisken C, Fiche M, Delorenzi M, Iggo R. Identification of molecular apocrine breast tumours by microarray analysis Oncogene 24, 4660-71(2005)

Chu, E.Y., Hens, J., Andl, T., Kairo, A., Yamaguchi, T.P., Brisken, C., Glick, A., Wysolmerski, J.J., Millar, S.E. Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131, 4819-29 (2004) full article [pdf]

Brisken, C., Socolovsky, M., Lodish, H. F., Weinberg, R.A. The Signaling Domain of the Erythropoietin Receptor Rescues Prolactin Receptor-Mutant Mammary Epithelium. Proc. Natl. Acad. Sci. USA 99, 14241-5 (2002)

Brisken, C., Ayyannan, A., Nguyen, C., Heineman, A., Reinhardt, F., Tan, J., Dey, S.K., Dotto, G. P., Weinberg, R.A. IGF-2 is a mediator of prolactin-induced proliferation/morphogenesis in the breast. Developmental Cell 3, 877-887 (2002)

Reviews

Tanos, T., Brisken, C. What signals operate in the mammary niche? Breast Disease 29: 69-82 (2008)

Brisken, C. Endocrine Disruptors and Breast Cancer. Chimia 62(5): 1-4 (2008)

Brisken, C., Duss, S. Hormones and the stem cell niche in the breast: a developmental perspective. Stem Cell Reviews. 3 (2): 147-156 (2007)

Brisken, C. and Rajaram, R.D. Alveolar and Lactogenic Differentiation. J Mammary Gland Biol. 11(3-4):239-48 (2006)

Gass, S., Harris, J., Ormandy, C., Brisken, C. Using expression arrays to elucidate the gene expression programs driving prolactin function. Journal of Mammary Gland Biology and Neoplasia 8, 269-286 (2003)

Brisken, C. Breast Cancer, Learning from the mouse mammary gland. Bull Suisse Cancer 1, 28-31 (2003)

Brisken, C., Ayyannan, A., Doppler, W. Prolactin signaling and Stat5, going their own separate ways? Breast Cancer Research 4, 209-212 (2002) full article [pdf]

Brisken, C. Hormonal control of alveolar development and its implications for breast carcinogenesis. Journal of Mammary Gland Biology and Neoplasia 7, 39-48 (2002)