Oncogenic Functions of cdK4 and cdK6
Abstract
Cancer cells often contain disruptions in the transition from GL phase to S phase. The retinoblastoma protein (pRb) is one negative regulator of cellular proliferation. Many breast cancers retain functional pRb and therefore must use other mechanisms to alleviate the tumor-suppressive function of pRb. One common mechanism to circumvent pRb function is amplification of the GL phase cyclin dependent kinases (cdk), cdk4 and cdk6. Cyclin dependent kinase 4 and cdk6 are thought to have redundant functions as pRb regulators, despite an increasing body of evidence suggesting that certain tumor types specifically activate either cdk4 or cdk6. This implies that either the function or the regulation of these kinases may be different in different cell types. Data presented here show that cdk4 and cdk6 have different abilities to drive the cell cycle-from GL into S phase in the osteosarcoma cell line, U2OS. Understanding differential regulation of these two kinases and their potentially different activation in response to mitogenic signals may eventually provide a mechanism to therapeutically interrupt kinase activity. Ability to interrupt kinase activity separate from cyclin Dl association ma rove an important intervention in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADB240661
Entities
People
- Martha J. Grossel
Organizations
- Harvard Medical School