Event
ISR Focus on Medicine Series: Ahmed Sultan, "Suppression Stategy for Breast Cancer"
Tuesday, December 16, 2008
2:00 p.m.
1146 A.V. Williams Building
Regina King
301 405 6615
rking@umd.edu
ISR Focus on Medicine Series
Active Jak2/Stat5 Signaling: A Suppression Strategy for Human Breast Cancer Invasion and Metastasis and a Potential for a New Differentiation Therapy
Ahmed S. Sultan M.D., Ph.D., M.P.H.
Department of Clinical Biochemistry & Molecular Biology
Alexandria University
Alexandria, Egypt
Host
Eyad Abed
Abstract
Poor prognosis of human breast cancer is associated with a high potential of cancer cell invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process.
We have recently uncovered novel evidence that signal transducers and activators of transcription 5a (Stat5a) and its Janus tyrosine kinase, (Jak2), suppress invasion and promote human breast cancer cell differentiation through inhibition of epithelial-to-mesenchymal dedifferentiation. However, the precise mechanism of the role of Jak2/Stat5a in human breast cancer is still under investigation.
In this study, we have further critically taken advantage of the combination of Jak2/Stat5a genes expression, HDAC inhibitors, and Mistletoe (Viscum album) plant extracts as an alternative way to suppress breast cancer progression by reversing the mesenchymal phenotype, and restoring homotypic adhesion, and in turn induce tumor differentiation in vitro and in vivo.
We have expanded our investigation to involve a highly invasive breast cancer cell line, MDA-231, in addition to BT-20 and T-47D human breast cancer cells that display different phenotypic and differentiation patterns ranging from poor to high differentiation. We have also established a xenograft tumor model of MDA-231 cells in nude mice for in vivo studies. After 4 weeks, the growth of MDA-231 tumors co-expressing Wt- Jak2/Stat5a was inhibited by 47.90% compared to the mock group (t=2.821, P<0.05) and by 52.86% compared to the tumors expressing Dn-Stat5 group (t=2.394, P<0.05). Furthermore, the pretreatment with HDAC inhibitors and/or Mistletoe (Viscum album) plant extracts enhanced significantly the growth inhibition of MDA-231 xenografted tumors expressing Wt-Jak2/Stat5a compared to the tumors expressing Wt-Stat5a or Wt-Jak2 alone.
Collectively, the observations support a novel role of Jak2/Stat5a genes as a new tool to restore lost differentiation of human breast cancer through inhibiting EMT that could lead to new therapeutic strategies to reverse cancer progression-related changes and introduce alternative cancer treatments in addition to standard chemotherapy and radiation treatment.
Ref.: Sultan, et al., Oncogene, 2005; Sultan, et al., Cancer Science, 2008.
Biography
Dr. Ahmed S Sultan received his MD/PhD from Osaka University School of Medicine in 1999. Afterwards, he received an M.P.H. from Georgetown University in 2005. His areas of interest include clinical biochemistry and molecular biology; gene therapy for breast and liver cancer, and the role of stem cells in cancer models. Currently, Dr. Sultan is Associate Professor of Clinical Biochemistry and Molecular Oncology at Alexandria University in Egypt, and an Appointed Associate Professor at Johns Hopkins University Medical Center.
