Triplex Forming Therapeutic Agents for Breast Cancer.
Annual rept. 15 Dec 93-14 Dec 94,
ALABAMA UNIV IN BIRMINGHAM
Pagination or Media Count:
The overall goal of this grant is to develop sequence specific DNA binding compounds which are targeted by triplex DNA formation to the promoters of the c-myc, neu, and c-Ha-ras genes. These genes play important roles in the malignant phenotype of breast carcinoma cells. During the past year, we have demonstrated that the major problem with the treatment of tumors in intact animals with TFOs is delivery of intact oligonucleotides to the nuclei of tumor cells. We have attempted to circumvent this problem by the creation of plasmids which express triplex forming transcripts. These plasmids appear to have significant anti proliferative characteristics. We have also cloned and sequenced a set of cDNAs complementary to RNA molecules which appear to regulate c-myc expression via triplex formation. We have also demonstrated that the nontranslated tumor suppressor gene, Hi 9, downregulates expression of the c-myc promoter. This gene also contains a sequence which is highly homologous to the triples forming region of the c-myc Pi promoter. We think that the discovery and characterization of triplex forming transcripts promises to lead to effective transcriptional Thhihitorv transcripts with potential as gene therapy vectors.
- Medicine and Medical Research