NM23 GENE-EXPRESSION IN HUMAN BREAST CARCINOMAS - LOSS OF CORRELATIONWITH CELL-PROLIFERATION IN THE ADVANCED PHASE OF TUMOR PROGRESSION

NM23 is a protein associated with tumor progression, expressed in all tissues and in human tumors. Reduced expression of NM23.H1 is related to high incidence of lymph node and distant metastasis or to poor prog nosis of the patient in several human malignant tumors. In this study we analyze NM23 expression in non-neoplastic mammary tissues surroundi ng the tumoral lesions, in human mammary carcinomas and in lymph node metastasis. Our analysis shows that NM23.H1 expression is lower in the mammary cells surrounding the tumor than in the tumor itself. In the primary tumors we observed a negative trend between degree of local in vasion and level of NM23.H1 expression. A further decrease of NM23.H1 was detected in the invasive tumors that metastasized to axillary lymp h nodes and in the metastasis. NM23.H2 was always more highly expresse d than NM23.H1, and reduced expression of NM23.H1 but not NM23.H2 was concordant with the presence of lymph node metastasis or local invasiv eness of the primary tumor. A positive correlation between NM23.H1 mRN A content and cell growth rate of breast tumor cells has been confirme d. However, this trend was not maintained in cancer cells from tumors that metastasized to axillary lymph nodes and in metastatic cells; in these 2 situations the NM23.H1 mRNA content varied without any relatio nship to the proliferative rate of the cells. In addition, in comparis on with the initial tumor, the metastatic cell population showed a str ong decrease of NM23.H1 expression and increased proliferative activit y. (C) 1997 Willy-Liss, Inc,.