PHORBOL 12-MYRISTATE 13-ACETATE ENHANCES NM23 GENE-EXPRESSION IN MURINE MELANOCYTES BUT NOT IN SYNGENEIC B16-BL6 MELANOMA VARIANTS

The nm23 gene has been described as a potential metastasis suppressor gene in certain rodent and human tumors. We previously demonstrated th at tyrosine and phenylalanine restriction suppresses metastatic hetero geneity of B16-BL6 murine melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigated nm23 e xpression in the highly metastatic B16-BL6 (ND) melanoma, its nutritio nally derived poorly metastatic (LT) variant, and the syngeneic non-tu morigenic Mel-ab melanocytes. No differences in nm23 expression were o bserved between ND and LT cells, and nm23 expression varied between di fferent isolates. Previously, we showed that metastatic potential of 1 -ND cells decreases and is not altered in 1-LT cells after prolonged i n vitro cell passage; however, nm23 expression is equivalently increas ed by 2-fold. In 2-ND and 2-LT cells, expression of nm23 is not differ ent at higher in vitro cell passage. Expression of nm23 decreased abou t 2-fold when phorbol 12-myristate 13-acetate (PMA) was removed from M el-ab cells, which induces these cells to become quiescent. Although m embrane-associated protein kinase C (PKC) activity decreased after pro longed PMA treatment in all cells, neither nm23 expression nor prolife ration of ND and LT cells was affected by PMA. These data indicate tha t nm23 expression is related to proliferative activity rather than to the suppression of metastatic potential. (C) 1996 Wiley-Liss, Inc.