Testing Clinical Relevance and Therapeutic Potential of a Novel Secreted Ligand of TNF Family
Abstract
LIGHT, a new member of TNF superfamily, is highly expressed in activated lymphocytes but not in cancer cells. Soluble LIGHT was proved to inhibit the growth of cancer cells expressing both LTBetaR and THVEM/TR2 receptors. Local LIGHT gene transfer suppresses in vivo tumor formation. The anti-cancer effect of LIGHT correlates with its up-regulation of intercellular adhesion molecule-1 (ICAM-l) expression of cancer cells. The up-regulation of ICAM-1 expression is not only at ICAM-1 protein trafficking level on cell surface as showed by flow cytometry analysis, but also at ICAM-1 total protein level as confirmed by Western blot. We further confirmed that LIGHT enhancement up-regulation of ICAM-1 expression is STAT1 and JAK1 dependent using STAT1 deficient U3A and JAK1 deficient E2A4 cells. LIGHT-induced apoptosis of cancer cells resulted in down-regulation of anti-apoptosis Bcl-2 family members, such as Bcl-2, Bcl-X(L), Bag-1, and Mcl-1; up- regulation of pro-apoptosis Bcl-2 family member Bak. Extensive caspase activation is required in LIGHT- induced apoptosis of HT-29 colon cancer cells, but may not be required for LIGHT-induced apoptosis of MDA- MB-231 breast cancer cell. Activation of both DFF45 and PARP are involved in LIGHT-induced apoptosis. It was also proved that Bcl-2 down-regulation by LIGHT is STAT1 dependent.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA424660
Entities
People
- Dajun Yang
Organizations
- Georgetown University