During the course of these studies, we discovered a novel gene, TIEG, that plays an important role in growth factor and steroid hormone regulation of cell proliferation and gene regulation in normal and cancer cells. We are examining the role of TIEG gene in normal bone cells and cancerous bone cells, as well as breast cancer cells. We have found that the TIEG gene represses gene activity, and its overexpression can inhibit cell division and cancer growth. In collaboration with Dr. Bill Tremaine and Dr. Bill Faubion, Gastroenterology, we are investigating defects in another steroid pathway, the glucocorticoids, to discover the cause of resistance in the treatment of ulcerative colitis and other bowel diseases. In collaboration with Dr. Jim Ingle , Oncology, and Dr. Khosla, we are investigating how breast cancer cells interact with bone cells to encourage breast cancer metastasis transfer or migration to the skeleton.
Skeletal metastasis is a major mortality factor of many types of cancers.
We are also examining novel bisphosphonate compounds to identify more effective drugs to prevent cancer metastasis to the skeleton. We have identified a paracrine factor, secreted by the breast cancer cells, which inhibits bone formation, and thereby encourages sites for metastasis. We have found that bisphosphonates block this activity, thus reducing cancer cell metastasis. Our studies could well result in the identification of new estrogen analogues and bisphosphonate analogues for the treatment of bone diseases osteoporosis and cancer metastasis to bone. Overall, the atmosphere, facilities, and financial support at Mayo have been major factors in the success of this research program.