The huntingtin interacting protein (HIP 1) is absent in normal prostate and colon epithelial cells, but it is found in large amounts in prostate, colon, and other tumor cells. The current work is the first to associate the protein with cancer.

"Anytime you find a true marker for cancer, it's surprising," says Theodora S. Ross, M.D., Ph.D. "But HIP1 also is unusual because it seems to be such a strong prognosticator, especially for prostate cancer."

"We don't find significant HIP1 expression in normal prostate epithelial cells, but as prostate cancer develops and progresses, we see a steady increase in HIP1 expression," Ross explains. "HIP1 was expressed in 50 percent of tumors from patients in the earliest stages of cancer, 88 percent of tumors from patients with localized prostate cancer, and 100 percent of patients with metastatic prostate cancer."

"High levels of HIP1 were present in every stage of colon cancer," Ross adds. "In melanoma, breast and ovarian cancers, the expression patterns varied, but HIP1 was consistently overexpressed."

Dr. Ross’s research has focused solely on the protein and its relation to an important cellular trafficking and signaling system called the clathrin-mediated trafficking pathway. Cells use this system to remove old receptors and signaling molecules on cell surfaces and replace them with new signaling molecules.

The HIP1 protein appears to be involved in this process, according to Ross, along with another protein called htt, which is expressed by the allele responsible for Huntington's disease. Although both proteins are found in parts of the cell where movement of material occurs, their exact roles are unknown. The connection to the Huntington's gene could be significant, however, "because people with Huntington's rarely get cancer," Ross adds.

"This is a new pathway in tumorigenesis; no one else is working with it in this context," Ross says. "Our paper is the first demonstration of a connection between tumor formation and a protein involved in this cell trafficking pathway."

Ross' laboratory is now trying to understand the relation between HIP1 and cancer cells. "Originally, I thought HIP1 was a tumor suppressor gene, but it could be a survival factor that prevents cancerous cells from dying or an oncogene causing normal cells to become cancerous. It could have varying effects, depending on the cell or tissue type. More research is needed to know for sure," she says.

If scientists can discover the functional relation between HIP1 and cancer, Ross believes it should be possible to develop agents that could kill prostate and colon tumor cells without harming the normal epithelial cells in the same tissues.