| Popis: |
Interferon alpha (IFN-α) represents an adjuvant therapy of proven effectiveness in increasing disease-free interval and survival in subgroups of melanoma patients. Since high doses of cytokine are required, the treatment is often accompanied by toxic side effects. In addition, naturally occurring insensitivity to IFN-α may hamper its therapeutic efficacy. Clinical, molecular or immunological markers enabling the selection of potential responders have not so far been identified. To explore the molecular basis of IFN-α responsiveness, we analyzed the expression pattern of about 7000 genes in IFN-α-sensitive and IFN-α-resistant cell lines using high-density oligonucleotide arrays. Melanoma cell lines were screened for their sensitivity to proliferation inhibition and HLA class I induction by IFN-α by standard 3H-thymidine incorporation and flow cytometry. Total cellular RNA from four sensitive and two resistant cell lines was extracted, reverse-transcribed and hybridized to high- density oligonucleotide arrays. The comparative analysis of gene expression in either set of cell lines allowed the identification of four genes (RCC1, IFI16, hox2 and hi9) preferentially transcribed in sensitive cells and two (SHB and PKC-0 preferentially expressed in resistant cells. |
