Role of CDK4 in Breast Development and Cancer
Abstract
Cdk4 is an important regulator of G1/S cell cycle progression in mammalian cells. In about 15.8% (15 out of 95) of breast cancers cdk4 gene was shown to be amplified and this amplification of cdk4 gene was correlated with high Cdk4 protein expression. Our studies with the breast tissues of cdk4 (neo/neo) mice revealed the presence of small fat pads and poor ductal branching when compared to that of wild type mice. In order to determine the importance of cdk4 in Wnt- and Neu-induced breast tumorigenesis we generated cdk4 (neo/neo): MMTV-transgenic lines that express Wnt and Neu in breast specific manner. Our results from these studies indicated that there is impaired lobuloalveolar compartment development and poor ductal branching in case of cdk4 (neo/neo): MMTV-neu mice when compared to cdk4 (+1+): MMTV-neu mice. In contrast the mammary gland development in case of both Wnt transgenic mice cdk4 (+1+): MMTV-Wnt and cdk4 (neolneo): MMTV-Wnt is comparable. Further studies revealed that there is resistance to neu-induced breast tumorigenesis in case of cdk4 (neo/neo): MMTV-neu mice when compared to cdk4 (+1+): MMTV-neu mice. In contrast in case of Wnt transgenic mice the tumorigenesis studies revealed that both cdk4 (+1+): MMTV-Wnt and cdk4 (neo/neo): MMTV-Wnt mice are equally susceptible to breast cancer induced by Wnt. This indicates that cdk4 is essential for neu-induced tumorigenesis and not for Wnt-induced tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA462437
Entities
People
- Haritha Reddy
Organizations
- Temple University