Protein Function in Cancer Biology

Research from the lab of Prof. Robert Sheaff

P27kip1 is a tumor suppressor protein that is commonly deregulated in aggressive human cancers. Understanding why could lead to better diagnostic and therapeutic approaches for treating these life threatening forms of the disease. It is well known that p27 can block cell cycle progression by inhibiting cyclin dependent kinases. It is unclear, however, whether this activity is sufficient to explain p27 tumor suppressing function. Previous work showed p27 also targets GRB2, thereby blocking activation of the proto-oncogene Ras. Breast cancer cell lines were analyzed to determine if this novel pathway was disrupted in the disease state. Results indicated that p27 targets GRB2 in untransformed breast epithelial cells, but this pathway was disrupted in breast cancer cell lines. Although p27 protein was present in the breast cancer cells, it failed to target GRB2 because it was sequestered by overexpressed cyclin D.