Characterization of a Novel Tumor Suppressor Gene, mda-7, and It's Ability to Induce Apoptosis
Abstract
Information on targets for anticancer therapy that are most likely to lead to cancer cell death and/or cessation of growth is necessary. Human melanoma cells exhibit irreversible growth arrest and terminally differentiate on treatment with recombinant human fibroblast intefferon-beta (lFN-beta) and a protein kinase C activator meserein (MEZ). To identify and characterize the milieu of gene expression alterations associated with growth arrest and differentiation we applied subtraction hybridization. One of the genes so identified is mda-7, a novel tumor cell specific, growth suppressor gene. Mda-7,gene expression is elevated in terminally differentiated human melanoma cells, however, ectopic expression of recombinant mda-7 initiates growth suppression and apoptosis. Interestingly this tumor growth suppression property of mda-7 is not limited to melanoma alone and is evident in diverse cancers of various origins and having different genetic alterations. Utilizing a replication deficient adenoviral vector, the tumor growth suppression/apoptosis induction property of mda-7 was studied with a view towards the development of a new experimental tumor gene therapeutic. When tested in vivo in nude mice, using both tumorigenesis and experimental gene therapy protocols, Ad.mda-7 S suppresses tumor growth and inhibits cancer progression. In contrast, no discernible biological effect is elicited by both normal human epithelial or fibroblast cells when infected with Ad.mda-7 S. The differential growth suppression activity of mda-7 towards cancer cells and its selective anti-tumor effects illustrate a novel class of cancer growth suppressor genes with great promise for targeted therapy of human cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA385389
Entities
People
- Malavi Madireddi
- Paul B Fisher
Organizations
- Columbia University