Several laboratories are pursuing the question of whether the expression of pigment genes can be used as a useful marker for tumour progression. However, many
melanoma tumours are amelanotic in vivo. The purpose of this study was to examine the relationship between the expression of
tyrosinase-related genes [
tyrosinase,
tyrosinase-related protein-1 (TRP-1) and
tyrosinase-related protein-2 (TRP-2)] and pigmentation of
melanoma cells. Fourteen cutaneous
melanoma cell lines were examined for visible pigment,
melanin content, and
dopa oxidase activity and findings were related to the previously determined expression of the three
tyrosinase-related genes in these cells in culture. Four of the cell lines were also stimulated with
alpha-MSH, isobutylmethylxanthine, and
forskolin to examine the relationship between induced pigmentation and upregulation of pigmentation genes. There was no simple correlation between pigmentation gene expression and
dopa oxidase activity or total
melanin content of the 14
melanoma cell lines in culture. In the majority of cells, there was no appreciable pigment, whereas, in contrast, half of the cells showed significant
dopa oxidase activity. Upregulation of
dopa oxidase activity was achieved by
alpha-MSH in two out of four cell lines examined in detail and with
IBMX in three out of four of these cell lines.
IBMX increased
tyrosinase gene expression in all four cell lines;
alpha-MSH was without effect; and
TRP-1 and TRP-2 expression were largely unaffected by
IBMX or
alpha-MSH. Modest changes in morphology were noted in response to
IBMX. Overall, however, human
melanoma cell lines were, with two exceptions, amelanotic in culture despite the fact that 10 out of the 14 lines expressed
tyrosinase-related genes. We conclude that measurable pigmentation is not a necessary consequence of the expression of pigmentation genes. An implication of this work is that amelanotic tumours in vivo may nevertheless be positive for
tyrosinase-related genes.