The Role of RB in the Therapeutic Response of Breast Cancer
Abstract
The retinoblastoma tumor suppressor protein (RB) participates in the growth regulation of breast cancer cells by controlling G-S phase progression and mediating cell cycle arrest in response to anti-mitogenic signaling. RB is functionally inactivated in nearly half of all breast cancers. Although RB loss has been implicated in the bypass of both DNA damaging and anti-estrogenic therapeutic pathways, studies of the impact of RB upon the therapeutic response of breast cancer have been limited. Thus, we belive that our analyses of RB function and its effect upon downstream targets in modifying the therapeutic response of breast cancer cells is imperative for the design of improved treatment strategies. We demonstrate using siRNA to Rb that is loss and subsequent target deregulation in MCF-7 cells contributes to resistance to anti-estrogen therapy and DNA damage checkpoint bypass following exposure to ionizing radiation (IR). Furthermore, microarray and proteomic analyses reveal that loss of cell cycle arrest following estrogen ablation in RB deficient cells is coupled with increased expression of downstream targets with respect to Rb-proficient controls. Taken together, our data reveal that RB loss in breast cancer facilitates cellular resistance to two major modes of breast cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA434063
Entities
People
- Emily E. Bosco
Organizations
- University of Cincinnati