Potential Role of a Novel Nuclear Matrix Protein (nmt 55) as a Tumor Marker in Human Breast Cancer Invasion and Metastases

The goal of this proposal is to test the hypothesis that loss of expression of a novel protein contributes to tumor growth, invasion and metastases, and its expression suppresses these biological events. We have identified, isolated and partially characterized a 55 kDa nuclear matrix protein from human breast tumor cells (hence forth referred to as nmt55). This novel protein is expressed in some estrogen receptor positive (ER+) tumors but was completely absent in ER tumors. Loss of expression of this novel protein correlated strongly with tumor size (pO.O3) and loss of ER and PR (pO.OO1). As the tumor size increased, the expression of nmt55 was not detected at the protein level. Because increased tumor size is associated with metastases, we postulate that loss of nmt55 expression is associated with molecular and cellular changes linked to cellular differentiation leading to loss of ER expression, and development of hormone-independent tumor growth, invasion and metastases. We have cloned the cDNA for nmt55 and generated site-directed polyclonal antibodies. We are currently investigating the function of nmt55 using biochemical and molecular biology approaches. The information derived from these studies will help determine the potential role of this novel nuclear matrix protein (nmt55) as a marker of tumor progression and metastases. These studies may provide critical information needed for early detection of potentially metastatic tumors, and improve diagnosis, prognosis and in developing strategies for therapeutic management and care of breast cancer patients.