|Randolph C. Elble, Ph.D.
Cancer Biology – Tumor Suppression
We are interested in a new are of cancer biology, tumor suppression by the recently discovered CLCA family of calcium-activated chloride channel regulators. We have isolated several members of this gene family from mouse and human and characterized their expression in normal and cancer cells. We find that in normal breast, the CLCA2 gene is strongly induced by master regulator p53 in response to multiple physiological stresses encountered by the evolving tumor cell, including cell detachment and DNA damage by chemotherapeutic agents. On the other hand, in breast cancer cells, the gene is downregulated, suggesting a role as a tumor suppressor. Accordingly, we find that cancer cells forced to express CLCA2 die by apoptosis, while normal cells cease dividing. We have established collaborations with multiple groups at SIU to investigate the role of CLCA2 in tumorigenesis, metastasis and normal development. In addition, we recently received funding from NCI to test the therapeutic potential of CLCA2 in cancer. In the longer term, and beyond the role of CLCAs in tumorigenesis, we are probing the structure and function of this mysterious family of proteins using the tools of molecular biology, genetics, genomics/proteomics, electrophysiology, biochemistry and cell biology.