The Role of GIRK in Breast Cancer and its Functional Association with Beta-Adrenergic Mediated Signal Transduction
 Howard Plummer, III
Ph.D., Bowling Green State University
Research Assistant Professor
Breast cancer is the leading cancer in women. Despite significant advances in early detection and treatment of breast cancer, a large proportion of cases demonstrate extensive metastatic spread, high relapse rate, and failure to respond to therapy. In particular, estrogen non-responsive breast cancers have a poor prognosis.
Most breast cancers develop in the glandular tissue; these cancers are classified as adenocarcinoma, a term applied to cancers of glandular tissue anywhere in the body. Dr. Plummer’s group, as well as other researchers, has shown that adenocarcinoma in lung, colon, and pancreas express beta-adrenergic receptors, which mediate a variety of cellular events, and that stimulation of these receptors leads to DNA synthesis. DNA synthesis is necessary for cells to replicate, and replication enables a cancerous tumor to continue growing.
The expression of beta-adrenergic receptors has been correlated with the overexpression of arachidonic acid-metabolizing enzymes, cyclooxygenase-2 (COX-2) and lipoxygenase in adenocarcinomas of lungs, colon, prostrate, pancreas, and breast. Recent studies in Dr. Plummer’s laboratory demonstrated that three estrogen-responsive and three estrogen non-responsive cell lines derived from human breast cancers exhibit a significant reduction in DNA synthesis when exposed to beta-blockers and inhibitors of COX-2 and lipoxygenase. Inhibiting DNA synthesis would prevent cells from replicating.
Dr. Plummer’s group has also found a functional link between the beta-adrenergic receptor pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in breast cancer cell lines, and the two pathways are involved in regulating the growth of these cancer cells. Current studies in Dr. Plummer’s laboratory are underway to determine the growth regulatory mechanisms stimulated by these pathways. Modulation of GIRK channels may be an important tool in diagnosis or treatment of breast cancers.
Results from Dr. Plummer’s studies will open avenues for the development of preventative approaches and treatments of breast cancer, particularly the estrogen non-responsive type of breast cancer. |
