| Popis: |
Of particular interest to breast cancer was the discovery that an area of chromosome 20q, known to be frequently amplified in breast cancer, harbored the gene for AIB1. AIB1 which stands for "Amplified in Breast cancer" codes for a protein which is a member of the steroid receptor coactivator (SRC) family. AIB1 is amplified in approximately 5-10% of breast cancers and the mRNA and protein overexpressed in >30% of breast cancers. AIB1 interacts with a superfamily of ligand activated nuclear receptors including the estrogen receptor (ER) and progesterone receptor (PR) to potentiate transcriptional activity leading to upregulation of downstream target gene expression. An important finding was that an isoform of AIB1 (delta3AIB1) is a significantly more effective coactivator of the estrogen receptor than AIB1 and is highly overexpressed in human breast cancer. Prior work in our lab showed that the downregulation of overall levels of AIB1 plus delta3AIB1, using a regulatable AIB1 directed ribozyme, resulted in reduced tumor growth in vivo. Overall, these data indicate a major role for AIB1 and its isoform delta3AIB1 in breast cancer development and growth. However the relative roles of AIB1 versus the more highly active delta3AIB1 in phenotypic changes in the breast has not been determined. |
