IFN unresponsiveness in LNCaP cells due to the lack of JAK1 gene expression Journal Article
| Authors: | Dunn, G. P.; Sheehan, K. C. F.; Old, L. J.; Schreiber, R. D. |
| Article Title: | IFN unresponsiveness in LNCaP cells due to the lack of JAK1 gene expression |
| Abstract: | We reported previously that 23% of human lung adenocarcinoma cell lines were unresponsive to IFN-γ. To extend this finding to cancer cells derived from distinct tissues of origin, we assessed IFN-γ receptor signaling in the LNCaP human prostate adenocarcinoma cell line, which in previous experiments by others failed to induce a range of IFN-dependent biological responses. In this report, we show that LNCaP cells fail to respond to either BFN-γ or IFN-γ because of an impairment in the proximal signaling events downstream of both IFN-γ and IFN-γ/β receptors that lead to the activation of STAT1. Furthermore, we show that INCaP insensitivity to the IFNs is a result of the absence of expression of the JAK1 kinase, an obligate component shared by both IFN-γ and IFN-α/β receptors. JAK1 was undetectable in INCaP cells at both protein and message levels. Treatment of LNCaP cells with a combination of inhibitors of DNA methyltransferases and histone deacetylases induced expression of JAK1 message. These results identify the molecular basis for IFN insensitivity in the LNCaP cell line and suggest that epigenetic silencing of key immunologic signaling components may be one mechanism by which tumor cells evade immune detection and elimination. ©2005 American Association for Cancer Research. |
| Keywords: | signal transduction; controlled study; human cell; histone deacetylase inhibitor; adenocarcinoma; stat1 protein; gene expression; cancer cell culture; cell line, tumor; transfection; prostatic neoplasms; tumor necrosis factor alpha; recombinant fusion proteins; recombinant gamma interferon; interferon-gamma, recombinant; enzyme inhibitors; rna, messenger; western blotting; immunoprecipitation; 5 aza 2' deoxycytidine; protein-tyrosine kinases; prostate adenocarcinoma; gene silencing; dna methyltransferase; gel mobility shift assay; histone deacetylases; trichostatin a; northern blotting; janus kinase 1; alpha interferon receptor; recombinant alpha interferon; gamma interferon receptor; beta interferon receptor; methyltransferase inhibitor; interferon type i, recombinant |
| Journal Title: | Cancer Research |
| Volume: | 65 |
| Issue: | 8 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2005-04-15 |
| Start Page: | 3447 |
| End Page: | 3453 |
| Language: | English |
| PUBMED: | 15833880 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 46" - "Export Date: 24 October 2012" - "CODEN: CNREA" - "Source: Scopus" |
