STUDY OF NM23 GENE-EXPRESSION IN AN N-METHYL-N-NITROSOUREA TRANSFORMED HUMAN BREAST EPITHELIAL-CELL LINE

In the present study we pinpoint the time of nm23 down-regulation duri ng the chemical transformation of the human breast epithelial cell lin e HBL100. The non-malignant HBL100 was transformed by exposing it to N -methyl-N-nitrosourea (MNU). We subsequently injected the transformed cells (HBL-T-MNU) into nude mice, resulting in tumor growth. With a se cond passage of these tumors in mice we observed lung and extra-region al node metastases. The expression of nm23 in the non-tumorigenic HBL1 00 cells was compared to the tumorigenic KBL-T-MNU cells as well as to the metastatic cell line HBL-T2(MNU) derived from the tumor induced b y HBL-T-MNU cells. By using immunohistochemistry and Western blot anal ysis we documented the downregulation of nm23 expression in the tumori genic HBL-T-MNU and metastatic HBL-T2(MNU) cell lines, as compared to the parental line HBL100. Once downregulated, nm23 expression in this model remains constant during the subsequent progression. These result s suggest that nm23 down-regulation may indeed be associated with earl y neoplastic transformation and is maintained throughout neoplastic pr ogression and metastatic stage.