Role of CDK4 in Breast Development and Cancer
Abstract
Cdk4 is an important regulator of G1/S cell cycle progression in mammalian cells. Loss of cdk4 in the mammary glands of mice results in abnormal development as evidenced by small fat pads and poor ductal branching. Deregulation of Ras signaling is seen in many cancers. The aim of this study is to determine the role of Cdk4 in Ras-induced breast tumorigenesis. Results presented in this study indicate that approximately 90% of cdk4 -/-: MMTV-v-Ha-ras mice remain resistant to v-Ha-ras-induced breast tumorigenesis while only 40% of their wildtype counterparts were found to be tumor-free. These studies also indicate that both cdk4 +/+: MMTV-v-Ha-ras mice and cdk4 (R24C/R24C): MMTV-v-Ha-ras mice induce Ras-driven breast tumors with the same frequency. Many of these tumors showed elevated levels of cell cycle proteins as well as increased levels and activity of Ras, Raf, MEK and ERK proteins. These results indicate that Cdk4 is important for v-Ha-ras-induced mammary tumorigenesis and that activating mutations in Cdk4 do not accelerate this process.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA471245
Entities
People
- Haritha Reddy
Organizations
- Temple University