Mechanisms of Rerg-Mediated Tumor Suppression in Breast Cancer
Abstract
Rheb (Ras Homolog Enriched in Brain), a member of the Ras family of GTPases, has been implicated as an oncogene and may be involved in estrogen-dependent breast cancer. Rheb activity is induced by non-genomic estrogen signaling; activated Rheb leads to activation of the mTOR kinase and increased protein translation and cell cycle progression. Whether Rheb is required for estrogen-induced breast cancer growth and whether Rheb can promote tamoxifen resistance has not been determined. The purpose of these studies was to determine the contribution of Rheb to the growth and progression of estrogen-dependent and tamoxifen-resistant breast cancers. Thus, I developed short hairpin RNA (shRNA) targeting Rheb1 to reduce its expression in MCF-7 breast cancer cells. Knocking down Rheb1 alone did not significantly affect estrogen-dependent cell proliferation, tamoxifen sensitivity, or anchorage-independent growth. However, it is possible that the closely related isoform Rheb2 may compensate for the loss of Rheb1 activity and thus complicate my results. These results suggest that inhibition of Rheb1 alone may not be beneficial treatments for breast cancer, but it remains possible that pharmacological agents targeting both Rheb1 and Rheb2 could show clinical activity in tumors with elevated Rheb activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2008
- Accession Number
- ADA508444
Entities
People
- Ariella B. Hanker
- Channing Der
Organizations
- University of North Carolina at Chapel Hill