Accession Number:

ADA374391

Title:

Oncogenic Functions of cdK4 and cdK6

Descriptive Note:

Annual rept. 1 Jul 1998-30 Jun 1999

Corporate Author:

HARVARD MEDICAL SCHOOL BOSTON MA

Personal Author(s):

Report Date:

1999-07-01

Pagination or Media Count:

68.0

Abstract:

Cancer cells often contain disruptions in the transition from G1 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 G1 phase cycling dependent kinases cdk, cdk4 and cdk6. Cdk4 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 G1 into S phase in the osteosarcoma cell line, U2OS and in primary mouse astrocytes. 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 cycling Dl association may prove an important intervention in breast cancer.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE