Kivonat:
Resistance to various antineoplastic agents is common in the
clinical management of malignant melanoma. The biological
mechanisms conferring these different drug-resistant phenotypes
are still unclear. To identify potential factors mediating drug
resistance to melanoma cells, the mRNA expression profiles of
the parental drug-sensitive human melanoma cell line MeWo and
four derived drug-resistant sublines with acquired resistance
against four commonly used drugs for melanoma treatment
(cisplatin, etoposide, fotemustine and vindesine) were analysed.
We investigated cDNA arrays with 43,000 cDNA clones (
approximately 30,000 unique genes) to study the expression
patterns of these cell lines. We were able to simultaneously
extract new candidate genes associated with drug resistance in
malignant melanoma and to correlate the present findings with
previously described resistance-associated genes. Using
hierarchical clustering and analysing the overlap of genes with
altered expression, we detected similarities between the
expression signatures related to cisplatin and fotemustine
resistance. The resistance against vindesine required a minimal
set of changes in gene expression relative to the parental MeWo
cell line. Our study provides new data that may be used to
obtain further insight into the resistance characteristics of
malignant melanoma.