The Regulation of JAB1 and Its Role in Breast Cancer
Abstract
The purpose of the research done has been to determine the mechanism for overexpression of JAB1 through transcription factor analysis and FISH as well as the role of JAB1 in Herceptin resistance. The major findings thus far are 1) The promoter region of JAB1 key transcription factors were identified that may drive JAB1 expression, C/EBP alpha, C/EBP beta, and STAT3. We found that STAT3 together with C/EBP alpha and beta greatly increase JAB1 transcription. We have evidence that both STAT3 and C/EBP bind to the JAB1 promoter. Further, that SRC is one key upstream activator of JAB1 transcription. 2) We have performed FISH on a number of breast cancer cell lines and patient fine needle aspirations and have seen amplification of the JAB1 locus 3) JAB1 overexpression confers resistance to Herceptin in breast cancer cell lines SKBR3 and BT474, and inhibition of JAB1 increased the efficacy of Herceptin mediated G1 arrest and p27 accumulation. Additionally, JAB1 was found to correlate with Herceptin resistance in human breast cancer tissue samples. We have completed nearly all of the tasks listed for this time period and are on track as indicated in the SOW.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2008
- Accession Number
- ADA519695
Entities
People
- Terry J. Johnson
Organizations
- The University of Texas MD Anderson Cancer Center