| Cancer Genomics and Signaling Section |
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Patrice Morin, Ph.D., Chief
Senior Investigator |
| Research Summary: Ovarian cancer is the fifth most common cause of cancer deaths among women in the U.S., yet very little is known about the molecular mechanisms involved in the development of this disease. In order to address this problem, we have completed a large-scale serial analysis of gene expression (SAGE) study in epithelial ovarian cancer. The analysis was aimed at two major problems in ovarian cancer: difficulty of detection and drug resistance. A better understanding of gene expression and pathways in ovarian cancer, as well as the changes in expression associated with drug resistance may lead to novel approaches for detection and therapy of this disease. |
| Identification and Dissection of Pathways Important in Ovarian Cancer: The myriad of genes abnormally expressed in ovarian cancer provides clues as to which molecular pathways may be relevant to ovarian tumorigenesis. We are using a variety of molecular biological tools to dissect the molecular pathways responsible for the aberrant gene expression. Of particular interest is the pathway involving the claudin tight junction proteins, which have been found consistently elevated in ovarian tumors. The identification and characterization of these pathways will provide a better understanding of ovarian cancer at the molecular level. |
| Identification of Ovarian Cancer-specific Biomarkers: In the past few years, we have examined gene expression in ovarian cancer and normal ovarian tissues using serial analysis of gene expression (SAGE). We have identified several thousand genes expressed in each tissue and found numerous genes differentially expressed between normal and malignant ovarian cells, including novel transcripts that we have named HOST (human ovarian-specific transcript). Genes whose expression is elevated in ovarian cancer, especially those that encode secreted and/or surface proteins may become targets for early diagnosis and various therapeutic strategies, such as immunotherapy. We are evaluating promising candidates and generating antibodies to investigate their clinical potential. |
| Analysis of Gene Expression Associated with Cisplatin Resistance: Resistance to chemotherapy is a major problem in the treatment of ovarian cancer, as half of the patients present with cisplatin-resistant tumors. In addition, many ovarian tumors initially responsive to treatment often become refractory to chemotherapy. In order to study this problem, we have created ovarian cancer cell lines that are resistant to cisplatin. Using this model, we have utilized SAGE to identify genes whose expression is altered in cisplatin-resistant cells. Among the genes differentially expressed in cisplatin-resistant cells, we have identified many genes encoding proteins of the extracellular matrix. We are interested in identifying the mechanisms of cell adhesion-mediated drug resistance (CAM-DR) in ovarian cancer. |
| Ovachip Manuscript |
| Sawiris, G.P., Sherman-Baust, C.A., Becker, K.G., Cheadle, C., Teichberg, D., Morin, P.J.: The Ovachip, a specialized cDNA array for the study and diagnosis of ovarian cancer. Cancer Research, 62: 2923-2928, 2002. |
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