Caspase Deficiency: Involvement in Breast Carcinogenesis and Resistance
Abstract
This project was proposed to study the correlation between caspase deficiency and breast cancer carcinogenesis and therapeutic resistance. In the last year of this grant, we examined the mRNA levels of 8 caspases in 20 breast cancer cell lines and the expression of caspases-3 in 102 cases of breast cancer tissues. We also studied the role of caspase-3 in genistein induced apoptosis. In summary of the whole project, we have examined the expression profiles of the majority members of the caspase family in 20 breast cancer cell lines and performed functional screening of these cell lines treated with different apoptotic stimuli. Our results indicated that caspase deficiency/down-regulation was frequently detected in breast cancer and suggested a correlation between caspase deficiency and breast carcinogenesis and therapeutic resistance. Using a caspase-3 specific model, we demonstrated that caspase-3 plays a critical role in the apoptosis of breast cancer cells. Deficiency of caspase-3 significantly impaired cellular response to various apoptotic stimuli, which contributed to therapeutic resistance. Sensitization of caspase-3 deficient cells by transfection of the caspase-3 gene suggests that caspase-3 gene therapy could be used to enhance therapeutic responses of refractory breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA428952
Entities
People
- Xiaohe Yang
Organizations
- University of Oklahoma Health Sciences Center