In Situ Evaluation of the Role of the Small GTPase Rac3 in Breast Cancer Metastasis

Abstract

We have made considerable progress towards testing the proposed hypothesis that the signaling proteins Rac3 and PAK are critical for the initiation of breast cancer metastasis. Stable fluorescent protein-tagged breast cancer cell lines expressing active and inactive forms of Rac3: MDA-MB-43 5 highly metastatic breast cancer cell line expressing dominant negative Rac3 and Hs578t non-metastatic breast cancer cell line expressing dominant active Rac3 have been created. We have analyzed these cell lines in vitro prior to in vivo analysis in a nude mouse model. As expected, metastatic cell lines expressing dominant active Rac3 demonstrate reduced migratory and adhesive properties. The non-metastatic breast cancer cell lines expressing dominant negative Rac3 demonstrate increased migratory and adhesive properties. We have initiated in vivo studies by injection of non metastatic breast cancer cells expressing Rac3(Tl7N) and the control cells into the mammary fat pads of female nude mice. We are currently monitoring for changes in metastatic efficiency. To provide a direct assessment of the functional consequences of activating or inhibiting Rac3, we have initiated the adaptation of a fluorescence confocal microscope to specifically image fluorescence cells inside live mouse tumors. We expect to first phase of our image analysis to begin in May 2003.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2003
Accession Number
ADA417031

Entities

People

  • Suranganie F. Dharmawardhane

Organizations

  • University of Texas at Austin

Tags

DTIC Thesaurus Topics

  • Anti-Bacterial Agents
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Movement
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Confocal Microscopy
  • Epithelial Cells
  • Fluorescence
  • Light Sources
  • Metastasis
  • Microscopes
  • Microscopy
  • Neoplasms

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Biology and Genetics
  • Nanoscale Plasmonic Nanotechnology