In the present study we pinpoint the time of nm23 down-regulation during the chemical transformation of the human breast epithelial cell line 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 second passage of these tumors in mice we observed lung and extra-regional node metastases. The expression of nm23 in the non-tumorigenic HBL100 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 by HBL-T-MNU cells. By using immunohistochemistry and Western blot analysis we documented the downregulation of nm23 expression in the tumorigenic 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 results suggest that nm23 down-regulation may indeed be associated with early neoplastic transformation and is maintained throughout neoplastic progression and metastatic stage.

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