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Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma.

Publication ,  Journal Article
Gollob, JA; Sciambi, CJ; Huang, Z; Dressman, HK
Published in: Cancer Res
October 1, 2005

IFN-gamma plays a role in the response to melanoma indirectly through its effect on the immune system and directly through its antiproliferative and proapoptotic effects on melanoma cells. To understand the molecular basis for the direct antimelanoma effect of IFN-gamma, we studied IFN-induced changes in gene expression and signaling among three human melanoma cell lines (DM6, DM93, and 501mel). These were resistant to the antimelanoma effect of IFN-alpha, and only DM6 cells exhibited growth inhibition and apoptosis with IFN-gamma. Through DNA microarray analysis, we found that the antimelanoma effect of IFN-gamma in DM6 was associated with the down-regulation of multiple genes involved in G-protein signaling and phospholipase C activation (including Rap2B and calpain 3) as well as the down-regulation of genes involved in melanocyte/melanoma survival (MITF and SLUG), apoptosis inhibition (Bcl2A1 and galectin-3), and cell cycling (CDK2). The antimelanoma effect of IFN-gamma was also associated with the up-regulation of the proapoptotic dependence receptor UNC5H2 and the Wnt inhibitor Dkk-1. Whereas both IFNs were able to activate Stat1 in all cell lines, the delayed activation of the extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinases occurred only in DM6 with IFN-gamma, and the effect of IFN-gamma on cell growth and survival as well as gene expression in DM6 was dependent on the coordinate activation of MEK1 and p38. These findings provide new insights into the signaling events and gene expression changes associated with growth inhibition and apoptosis in melanoma and may thereby assist in identifying new targets for the treatment of melanoma.

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Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

October 1, 2005

Volume

65

Issue

19

Start / End Page

8869 / 8877

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Wnt Proteins
  • Signal Transduction
  • Recombinant Proteins
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Melanoma
  • MAP Kinase Kinase 1
  • JNK Mitogen-Activated Protein Kinases
  • Interferon-gamma
 

Citation

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MLA
NLM
Gollob, J. A., Sciambi, C. J., Huang, Z., & Dressman, H. K. (2005). Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma. Cancer Res, 65(19), 8869–8877. https://doi.org/10.1158/0008-5472.CAN-05-1387
Gollob, Jared A., Catherine J. Sciambi, Zhiqing Huang, and Holly K. Dressman. “Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma.Cancer Res 65, no. 19 (October 1, 2005): 8869–77. https://doi.org/10.1158/0008-5472.CAN-05-1387.
Gollob JA, Sciambi CJ, Huang Z, Dressman HK. Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma. Cancer Res. 2005 Oct 1;65(19):8869–77.
Gollob, Jared A., et al. “Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma.Cancer Res, vol. 65, no. 19, Oct. 2005, pp. 8869–77. Pubmed, doi:10.1158/0008-5472.CAN-05-1387.
Gollob JA, Sciambi CJ, Huang Z, Dressman HK. Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma. Cancer Res. 2005 Oct 1;65(19):8869–8877.

Published In

Cancer Res

DOI

ISSN

0008-5472

Publication Date

October 1, 2005

Volume

65

Issue

19

Start / End Page

8869 / 8877

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Wnt Proteins
  • Signal Transduction
  • Recombinant Proteins
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Melanoma
  • MAP Kinase Kinase 1
  • JNK Mitogen-Activated Protein Kinases
  • Interferon-gamma