Roles of the CDK Inhibitors p27Kip1 and p57Kip2 in the Development of Breast Cancer

Abstract

Overexpression of the HER2/neu oncogene is found in approximately 30% of breast cancers. The mechanism behind which overexpression of HER2/Neu promotes cell growth is still unclear. We have found that HER2/neu oncogenic signals are able to downregulate the expression levels of p27KiP1 and p57KiP2 proteins. Immunohistochemistry studies showed that the expression of p27KiPl is remarkably decreased in metastasized breast tumor cells. Moreover, the low expression level of p27KiP1 in the HER2/neu activated B104-1-l cells can be reversed by introducing the dominant negative Grb2 construct (DeltaN- Grb2). Finally, using pulse-chase analysis and in vitro degradation assays we have shown that HER2/neu% status or activity indeed affects the protein stability of p27KiPl and p57KiP2 via ubiquitination pathway.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 1999
Accession Number
ADB257429

Entities

People

  • Heng-yin Yang

Organizations

  • The University of Texas MD Anderson Cancer Center

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Antibodies
  • Biological Staining And Labeling
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Degradation
  • Diseases And Disorders
  • Immunohistochemistry
  • Laboratory Animals
  • Materials
  • Neoplasms
  • Proteins
  • Recombinant Dna

Fields of Study

  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.