Targeting Transcription Elongation Machinery for Breast Cancer Therapy
Abstract
This project focuses on the important but under-studied role of the P-TEFb-dependent transcription elongation machinery in human breast cancer progression. It aims to test the hypothesis that transcription elongation is a key regulatory step in breast cancer development, and that targeting P-TEFb can be an effective strategy to block breast cancer progression. During the current reporting period, we have made significant progress toward the identification of the ELL2-containing SEC as the form of active P-TEFb that plays a key role in promoting breast cancer cell EMT. Through disrupting the negative P-TEFb complex, the 7SK snRNP, by targeted knockdown of HEXIM1 expression, we found that the KD not only promotes EMT but also enhances the interaction of CDK9 with HSP90, which has been strongly implicated in tumorigenesis. With this new information, we are investigating the mechanisms and significance of the ELL2-SEC and the CDK9-HSP90 complex in controlling the expression of key EMT and stemness regulators to accomplish the stated goals of the project in the next reporting period.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2017
- Accession Number
- AD1035590
Entities
People
- Qiang Zhou
Organizations
- University of California, Berkeley