Several genes implicated in the development of various
malignancies appear to be of minor relevance in
melanoma. We therefore aimed to find a tumour suppressor candidate involved in this
malignancy by comparing gene expression in uncultured primary
melanoma specimens with those in acquired melanocytic naevi, from which quite often
melanomas are known to arise. Applying the subtractive suppression hybridization technique, we generated a subtracted library of candidate genes downregulated in
melanoma. Among the
cDNA fragments identical to known genes, this library included a
cDNA fragment 630 bp in length that is identical to the gene for the human
protein phosphatase 2A (PP2A) regulatory subunit B (B56) gamma
isoform (PP2A-Bgamma, PPP2R5C). On further evaluation of 15 primary
melanoma and 16 acquired melanocytic naevus tissue specimens from independent patients using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, expression of this gene was found to be suppressed in
melanomas compared with naevi; the difference was statistically significant. As PP2A is known to be a major cellular
serine-threonine phosphatase, and has been implicated not only in the regulation of cell growth and division but also in the control of gene transcription and
growth factor signal transduction, alterations in the pattern of the regulatory subunits may affect substrate specificity and subcellular localization of the PP2A
holoenzyme in
melanoma cells.