title: Identification of differentially expressed genes in human melanoma cells with acquired resistance to various antineoplastic drugs.
abstract: Malignant melanoma displays strong resistance against various antineoplastic drugs. The mechanisms conferring this intrinsic resistance are unclear. To better understand the molecular events associated with drug resistance in melanoma, a panel of human melanoma cell variants exhibiting low and high levels of resistance to 4 commonly used drugs in melanoma treatment, i.e., vindesine, etoposide, fotemustine and cisplatin, was characterized by differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Of 269 mRNA fragments found to be altered in expression level by DDRT-PCR, a total of 11 cDNA clones was characterized after confirmation of a differential expression pattern by Northern blot analyses. These clones include 3 genes (DSM-1, DSM-3 and DSM-5) of known function, 4 previously sequenced genes (DSM-2, DSM-4, DSM-6 and DSM-7) of uncharacterized function and 4 novel genes (DSM-8-DSM-11) without match in GenBank. All of these genes exhibited altered mRNA expression in high level etoposide-resistant cells, whereby 7 genes (DSM-1-DSM-6 and DSM-8) were found to be decreased in the transcription rate in these etoposide-resistant cells. The mRNA synthesis of the remaining genes (DSM-7 and DSM-9-DSM11) was enhanced in high level etoposide-resistant melanoma cells. The expression of 5 (DSM-5 and DSM-7-DSM-10) of the cloned cDNA encoding mRNAs was modulated in various independently established drug-resistant melanoma cells, indicating to be associated with drug resistance. Further characterization of these genes may yield inside into the biology and development of drug resistance in malignant melanoma.
authors.affiliation: Institute of Pathology, Charité, Campus Mitte, Humboldt University Berlin, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Grottke
authors.forename: K
authors.initials: K
authors.lastname: Mantwill
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
authors.forename: H
authors.initials: H
authors.lastname: Lage
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000633:toxicity*; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D005819:Genetic Markers; D005047:Etoposide