Accession Number:

ADA516566

Title:

Unraveling the Molecular Mechanism(s) Underlying ER+/PR- Breast Tumorigenesis Using a Novel Genetically Engineered Mouse Model

Descriptive Note:

Annual rept. 1 Sep 2008-31 Aug 2009

Corporate Author:

MICHIGAN STATE UNIV EAST LANSING

Personal Author(s):

• Xiao, Hua

Report Date:

2009-09-01

Pagination or Media Count:

8.0

Abstract:

Estrogen-receptor alpha ER-positive Progesterone receptor negative ERPR- 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 mechanisms underlying ERPR- breast tumorigenesis. Specifically, we proposed to determine genetic and epigenetic alterations in the initiation and progression of ERPR- mammary tumors arising in Tip30--MMTV-neu mice. Here we show that Tip30 deletion in MMTV-Neu mice significantly accelerates the formation of ERPR- mammary tumors. An unbiased DNA microarray analysis revealed that Tip30 deletion resulted in increased activation of cAMP-mediated signaling, EGF signaling, IGF signaling and PI3KAKT signaling in ERPR- 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.

Descriptors:

• *BREAST CANCER
• HUMANS
• NEOPLASMS
• DEOXYRIBONUCLEIC ACIDS
• MOLECULAR BIOLOGY
• SENSE ORGANS
• MAMMARY GLANDS
• ANATOMICAL MODELS
• PROGESTERONE
• DYSPLASIA
• ACTIVATION
• MICE

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE