Nuclear Tubulin: A Novel Target for Breast Cancer Chemotherapy

Abstract

Our research is based on our finding that the beta (II) isotype of tubulin is found in the nuclei of breast cancer cells. Our goals are to learn the function of nuclear beta (II) and to design a novel anticancer drug to target it. We have found that beta (II) occurs in the nuclei of human breast tumor cells in situ but not in normal cells. Using cultured breast cancer cells, we have found a correlation between the presence of nuclear beta (II) and the presence of estrogen receptor. We have also found that breast cancer cells which do not have nuclear beta (II) in culture, acquire it after implantation into mice. This implies that the nuclear localization of beta (II) is under hormonal control with the likely hormone being estrogen. We have also found that the distribution of nuclear beta (II) is correlated with resistance to taxotere. In another cell type, we have found that nuclear beta (II) co-localizes with vault ribonucleoprotein, which is involved in drug resistance, estrogen receptors and nucleocytoplasmic transport. We have also synthesized a peptide which rapidly enters the nucleus; we are in the process of coupling that peptide to an anti-tubulin drug to test our first antitumor drug which targets nuclear beta (II).

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Document Details

Document Type
Technical Report
Publication Date
May 01, 1999
Accession Number
ADB257408

Entities

People

  • Richard F. Luduena

Organizations

  • University of Texas Health Science Center at San Antonio

Tags

DTIC Thesaurus Topics

  • Animals
  • Biological Staining And Labeling
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cells
  • Chemistry
  • Chemotherapy
  • Connective Tissue Cells
  • Cultured Cells
  • Cytoplasm
  • Drug Resistance
  • Laser Dyes
  • Neoplasms
  • Organelles
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Biology
  • Physics

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).