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SRI Profiles

Arun Seth, MS, PhD

Senior scientist

Sunnybrook Health Sciences Centre
2075 Bayview Ave., Room S2 38
Toronto, ON
M4N 3M5

Phone: 416-480-6100, ext. 3536
Fax: 416-480-5737

Administrative Assistant: Melanie Suttar (S1 10A)
Phone:
416-480-6100, ext. 3536
Email:
melanie.suttar@sunnybrook.ca

Education:

  • MS, 1975, organic chemistry, Meerut University, India
  • PhD, 1981, molecular biology, University of New Brunswick, Canada

Appointments and Affiliations:

  • Senior scientist, Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute
  • Director, molecular diagnostics and research, department of anatomic pathology, Sunnybrook Health Sciences Centre
  • Academic director, Centre for Genomic Studies, Sunnybrook Research Institute
  • Professor, laboratory medicine and pathobiology, University of Toronto
  • Professor, CIHR Group in Matrix Dynamics, faculty of dentistry, University of Toronto
  • Adjunct professor, College of Medicine, Medical University of South Carolina, USA

Research Summary:

Breast and prostate cancer: The major focus of our research is to understand the molecular mechanisms of breast and prostate cancer progression and metastasis better. We are using novel mouse models and molecular approaches to develop molecular therapeutic strategies that will interfere with the function of key proteins affecting these cancers.

Breast cancer functional genomics and predictive molecular pathology: Over the past decade, our laboratory has focused on studying breast cancer genome anatomy to characterize molecular targets that have diagnostic and therapeutic applications. We have isolated a number of novel genes associated with the ubiquitin mediated protein degradation pathway. The ubiquitin-proteasome pathway plays a major role in the degradation of many proteins involved in cell cycle, proliferation, apoptosis and progression and metastasis of breast cancer. Currently, we are characterizing the role of two RING E3 ligases BCA2 and RNF11 that appear to affect the regulation of key tumour suppressors and oncogene proteins via the ubiquitin-proteasome pathway. Our molecular analyses have shown that RNF11 also has important roles in TGF-ß signaling and BCA2 is involved in EGFR mediated signaling. Ongoing characterization of targets of BCA2 and RNF11 E3 ligases will provide potential therapeutic targets for breast cancer treatment.

An “all human” mouse model to study breast cancer metastasis to human bone: Patients with advanced breast cancers almost always develop bone metastases and for most patients originally diagnosed with breast cancer, the bulk of the tumour burden at time of death is in the bone. In support of that we have created an “all human” NOD/SCID mouse model in which he breast tumour cells and bone the target of osteotropic metastasis are both of human origin. This mouse model explicitly investigates the bone metastatic behavior of human breast tumours, and provides us with a functional assay discriminating between breast cancers with and without the potential to metastasize to bone. Genes expressed in human tumour samples that grow and metastasize to human bone implants and genes expressed in breast tumours that fail to grow are compared to each other by microarray analysis. By examining the gene expression pattern of the primary tumours, we are able to identify expression signatures that may predict the potential of primary breast cancer to metastasize to bone. Our mouse model and genome-based analysis will provide new insights into understanding the biology of breast cancer-bone metastasis and opportunity for the development of new and more effective methods/drugs for the treatment and prevention of bone metastatic breast cancer.

ETS gene translocations as biomarkers of prostate cancer: In some prostate cancers, we have identified that part of the TMPRSS2 gene that is normally activated by the male sex hormone androgen is translocated upstream of a cancer related ERG gene. Thus the resulting TMPRSS2:ERG fusion gene becomes abnormally active in response to androgen, but only in prostate cancer not in benign tissue. It is therefore a potential marker of malignancy. Our future research is designed to test whether screening for this gene in patient blood and tumour samples could predict progression and metastasis of prostate cancer which will be of great utility in aiding clinical management for cancer patients.

Selected Publications:

See current publications list at PubMed.

  1. Nofech-Mozes, S, Spayne, J, Rakovitch, E, Kahn, HJ, Seth, A, Pignol, J, Lickley, L, Paszat, L, Hanna, W: Biological Markers Predictive of Invasive Recurrence in DCIS. Clinical Medicine: Oncology. 2: 7-18, 2008.
  2. Nam, RK, Sugar, L, Yang, W, Srivastava, S, Klotz, LH, Yang, L, Stanimirovic, A, Enciou, E, Loblaw, DA, Trachtenberg, J, Narod, SA and Seth, A: Expression of the TMPRSS2:ERG Fusion Gene Predicts Cancer Recurrence after Surgery for Localized Prostate Cancer, British Journal of Cancer, 17;97(12):1690-5. 2007.
  3. Nam, RK, Sugar, L, Wang, Z, Yang, W, Kitching, R, Klotz, LH, Venkateswaran, V, Narod, SA, Seth, A: Expression of TMPRSS2 ERG Gene Fusion in Prostate Cancer Cells is an Important Prognostic Factor for Cancer Progression, Cancer Biology and Therapy, 6 (1): 40-5, 2007.
  4. Yang, W, Lam, P. Kitching, R, Kahn, HJ, Yee, A, Aubin, JE, Seth, A: Breast Cancer Metastasis in a Human Bone NOD/Scid Mouse Model, Cancer Biology and Therapy 6(8): 1289-94, 2007.

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