Induction of Radiosensitization by Antisense Oligonucleotide Gene Therapy
Abstract
Protein kinase C (PKC) participates in a variety of cellular processes. As a regulator of signal transduction pathways which control cell proliferation and death and as the primary intracellular receptor for tumor promoting phorbol esters, PKC represents a potentially important molecular target for anti-cancer therapeutics. PKC is a family of serine/threonine kinases composed of twelve unique isoforms. Relatively little information exists pertaining to the functions of individual PKC isoforms in breast cancer. However, PKC has previously been shown to have increased activity and expression in breast cancer versus normal mammary tissue (O'Brian et al., 1989; Gordge et al., 1996). The focus of the present study was on identifying specific PKC isoforms that facilitate breast tumor cell survival. Gamma radiation was used to challenge survival of the breast tumor cells in these studies because the results of earlier experiments with the PKC inhibitors, staurosporine, sangivamycin and H7 provided evidence that PKC inhibition increased radiation sensitivity (Begemann et al., 1998; Hallahan et al., 1992; Zhang et al., 1993). Antisense oligonucleotide technology was utilized to achieve isoform selective PKC inhibition. Alternative approaches to isoform selective inhibition included small molecule enzyme activity inhibitors and plasmid vectors that encode dominant negative mutant forms of PKC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADB284370
Entities
People
- Meredith A. Mccracken
Organizations
- West Virginia University