Unraveling the Molecular Mechanism(s) Underlying ER+/PR- Breast Tumorigenesis Using a Novel Genetically Engineered Mouse Model
Abstract
Estrogen-receptor alpha (ER?)-positive Progesterone receptor negative (ER+/PR-) breast ductal carcinomas comprise approximate 15-25% of human breast cancers. However, molecular mechanisms underlying the development of this subtype of breast cancer remain poorly understood. Using genetically-engineered Tip30 knockout mice generated in our laboratory, we previously demonstrated that Tip30 deletion results in development of tumors in several tissues and ductal hyperplasia in the mammary glands. This project is to study the molecular mechanism(s) underlying ER+/PR- breast tumorigenesis. Specifically, we proposed to determine genetic and epigenetic alterations in the initiation and progression of ER+/PR- mammary tumors arising in Tip30-/-/MMTV-neu mice. Here we show that Tip30 deletion in MMTV-Neu mice significantly accelerates the formation of ER+/PR- mammary tumors. An unbiased DNA microarray analysis revealed that Tip30 deletion resulted in increased activation of cAMP-mediated signaling, EGF signaling, IGF signaling and PI3K/AKT signaling in ER+/PR- mammary tumors. Taken together, our data suggest that inactivation of TIP30 may contribute to the development of ER-positive and PR- negative breast cancers through activation of EGF and IGF signaling pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2009
- Accession Number
- ADA516566
Entities
People
- Hua Xiao
Organizations
- Michigan State University