NM23 AND BREAST-CANCER METASTASIS

The majority of breast cancer patients succumb to metastatic disease. We summarize published and recent research concerning the nm23 gene in breast cancer metastasis. In a murine developmental study, nm23 expre ssion increased with the functional differentiation of the mammary gla nd in nulliparous and pregnant animals. In human breast cancer, five s tudies have now demonstrated a significant association between reduced nm23 expression, at the RNA or protein levels, and aggressive tumor b ehavior. Nm23-negative tumor cells have been observed in comedo ductal carcinoma in situ lesions in two independent studies, indicating that decreases in nm23 expression begin prior to actual histologically ide ntifiable invasion. Transfection studies, in which human mm23-H1 cDNA was expressed in the metastatic human MDA-MB-435 breast carcinoma cell line, indicate that nm23-H1 suppresses in vivo metastatic potential b y 50-90%. Finally, our data in melanoma and breast carcinoma transfect ion systems suggest that the biochemical mechanism of nm23 suppressive activity is likely not due to its nucleoside diphosphate kinase activ ity, association with GAP proteins, or secretion from cells.