Mechanisms for Controlling Breast Cancer Growth and Skeletal Metastasis

Abstract

Bone morphogenetic protein-2 (BMP-2), a potential growth factor for osteogenesis, inhibited estrogen-responsive growth of MCF-7 breast cancer cells. The mechanism involved inhibition of estrogen-induced mitogen activated protein kinase (MAPK) activity by BMP-2. BMP-2 also inhibited cell cycle progression in MCF-7 cells by increasing the level of a cyclin dependent kinase (CDK) inhibitor (CKI), namely, p2l. This in turn resulted in inhibition of CDK activities which inhibited phosphorylation of retinobastoma protein (pBb). pBb phosphorylation is tightly linked with its activity in cell cycle progression. Thus by inhibiting pRb phosphorylation BMP-2 arrested the cell cycle at the Gl phase and thus inhibited uncontrolled proliferation of these cells. In order to extend this finding in a clinical background we are now establising animal models of human breast cancer cell growth in which we are going to express BMP-2 under a tetracyclin regulatable promoter in the breast cancer cells. We have generated cell lines using these expression plasmids and have started to characterize them. We will also analyze breast cancer tissue samples for the expression of BMP-2 and its receptors. Once the analysis is complete, we will categorize the cancer samples in terms of their growth and metastasis property.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 2000
Accession Number
ADA383097

Entities

People

  • Nandini Ghosh-choudbury

Organizations

  • University of Texas Health Science Center at San Antonio

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Genetics
  • Growth Factors
  • Health Services
  • Inhibition
  • Inhibitors
  • Neoplasms
  • Osteogenesis
  • Peptide Growth Factors
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Immunology and Pathology
  • Molecular Biology and Genetics