Effects of α-difluoromethylornithine on markers of proliferation, invasion, and apoptosis in breast cancer

Elzbieta Izbicka, Robert T. Streeper, I. Tien Yeh, Oredius Pressley, Michael Grant, J. Valerie R. Andrews, Joseph Kuhn, Joyce O'Shaughnessy

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Aim: To examine changes in biomarkers expressed in breast tumors in response to patient treatment with the polyamine synthesis inhibitor α-difluoromethylornithine (DFMO). Patients and Methods: The expression of Ki-67 (MIB-1), matrix metalloproteinases (MMP) 2 and 9, urokinase-type plasminogen activator (uPA) were examined by immunohistochemistry in breast tissue specimens (controls: n=15, 13 evaluable, and DFMO group; n=27, 21 evaluable). Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Results: Significant increases in apoptosis, MMP-9 and uPA (tumor) were observed in 7 patients ≥50 years who received DFMO for ≥14 days relative to patients <50 years and/or who received <14 days of treatment (n=11). No other measured characteristics, including tumor estrogen and progesterone receptor status, hormone replacement therapy history, histopathological characteristics or tumor grade were correlated with these biomarker changes. Conclusion: Unexpected correlation of proapoptotic DFMO activity in postmenopausal women with breast cancer warrants further study.

Original languageEnglish (US)
Pages (from-to)2263-2269
Number of pages7
JournalAnticancer Research
Volume30
Issue number6
StatePublished - Jun 1 2010

Keywords

  • α-difluoromethylornithine
  • Apoptosis
  • Biomarker
  • Breast cancer
  • DFMO
  • Invasion
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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