Transcriptional program associated with IFN-α response of renal cell carcinoma Journal Article
| Authors: | Banerjee, D.; Chadalavada, R. S. V.; Bourdon, V.; Korkola, J. E.; Motzer, R. J.; Chaganti, R. S. K. |
| Article Title: | Transcriptional program associated with IFN-α response of renal cell carcinoma |
| Abstract: | Metastatic renal cell carcinoma (RCC) is refractory to therapy; however, 10%-20% of patients respond favorably with interferon-α (IFN-α) treatment. To understand the molecular basis of response to IFN-α therapy, we performed global gene expression analysis of sensitive and resistant RCC cell lines in the absence and in the presence of IFN-α, using high-density oligonucleotide arrays to detect differentially expressed genes. In the absence of IFN-α, no significant differences in gene expression were observed between six sensitive and six resistant cell lines. Gene expression analysis following a time course of IFN-α2b treatment in one sensitive (SK-RC-17) and one resistant (SK-RC-12) cell line revealed that 484 and 354 transcripts, respectively, were modulated. A considerable number of these transcripts were similarly modulated between the two cell types that included several known targets of IFN signaling associated with antiviral and immunomodulatory activity. A further analysis of gene expression pattern in response to IFN revealed that several transcripts associated with proapoptotic function were upregulated in the sensitive cells. In the resistant cells, transcripts associated with cell survival and proliferation were induced, and key apoptotic molecules were suppressed. This study suggests that the IFN-α response of individual RCC tumors is determined by the expression pattern of genes in the apoptosis vs. survival and proliferation pathways rather than by alterations in expression of one or more individual genes. © Mary Ann Liebert, Inc. |
| Keywords: | mitogen activated protein kinase; controlled study; human cell; carcinoma, hepatocellular; liver neoplasms; cell proliferation; cell death; cell survival; protein bcl 2; reverse transcription polymerase chain reaction; apoptosis; gene expression; gene expression profiling; fas antigen; gene function; immunoglobulin enhancer binding protein; transcription, genetic; cancer cell culture; dose-response relationship, drug; drug resistance, neoplasm; cell line, tumor; protein p53; kidney carcinoma; fibroblast growth factor 2; gene expression regulation, neoplastic; kinetics; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; cell culture techniques; immunomodulation; dna microarray; up-regulation; gamma interferon inducible protein 10; cell cycle regulation; dna methyltransferase 1; antiviral activity; somatomedin binding protein 3; interferon-alpha; transcription factor fkhr; protein kinase c alpha; frizzled protein; transcription factor runx1; cyclin dependent kinase 2; recombinant alpha2b interferon; growth arrest and dna damage inducible protein 153; rna isolation; osteonectin; protein bak; bh3 protein; biological response modifiers; protein c jun; protein noxa; 4 [5 (4 methyl 1 piperazinyl)[2,5' bi 1h benzimidazol] 2' yl]phenol; suppressor of cytokine signaling 1; uncoupling protein 2 |
| Journal Title: | Journal of Interferon and Cytokine Research |
| Volume: | 26 |
| Issue: | 3 |
| ISSN: | 1079-9907 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2006-03-01 |
| Start Page: | 156 |
| End Page: | 170 |
| Language: | English |
| DOI: | 10.1089/jir.2006.26.156 |
| PUBMED: | 16542138 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 4 June 2012" - "CODEN: JICRF" - "Source: Scopus" |
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