OVEREXPRESSION OF THE MYRISTOYLATED ALANINE-RICH C-KINASE SUBSTRATE IN HUMAN CHOROIDAL MELANOMA-CELLS AFFECTS CELL-PROLIFERATION

Reduced expression of the myristoylated alanine-rich C kinase substrat e (MARCKS) has been described in various cell lines after oncogenic or chemical transformation, leading to the question of whether this prot ein may be involved in cell proliferation, Here we compare the express ion of MARCKS in human tumor-derived choroidal melanoma cells (OCM-1) and in primary cultures of normal choroidal melanocytes, We found an i mportant down-regulation of the protein in the melanoma cell line, Sta ble transfection of these cells with the cDNA coding for MARCKS led to the selection of several clones expressing variable levels of the pro tein, Proliferation experiments performed with four of these clones re vealed that cell growth was reduced by 35-40% when compared with contr ol cells, Upon serum starvation, cell proliferation was almost abolish ed when the expression level of MARCKS was high, whereas it was only p artially reduced in the controls, MARCKS overexpression induced a high er percentage of cells in the G(0)-G(1) phase of the cell cycle upon s erum starvation, as well as the inhibition of colony formation in soft agar. Finally, the expression of the CDK inhibitor p27 was increased in the cells presenting a high Level of MARCKS protein, Altogether, th ese data suggest that the expression of this protein kinase C substrat e affects the proliferation and partially reverts the transformed phen otype of the OCM-1 cells.