Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy

Gary Guishan Xiao, Bing Sen Zhou, George Somlo, Jana Portnow, Agnes Juhasz, Frank Un, Helen K Chew, David R Gandara, Yun Yen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: The expression and activity of ribonucleotide reductase (RR) has been associated with resistance to multiple drugs in human cancer. The use of antisense oligonucleotide drug, GTI-2040, a 20-mer phosphorothioate oligonucleotide complemented to the human RR M2 subunit mRNA, represents an effective strategy for inhibiting RR. The increased specificity due to the anti-resistance effect of GTI-2040 may also lead to a more favorable therapeutic outcome. Materials and Methods: To understand the molecular mechanism underlying RR inhibition, patients' blood samples were analyzed using multiple dimensional proteomics technology via matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry. Results: A major difference occurred at 5k mlz in the MALDI profile, which appeared only in the non-responsive group and diminished after GTI-2040 treatment. This specific peptide peak remained at the basal level in responsive patients. The peak was identified to represent the F-box/LLR-repeat protein 17 (FBXL17) through nanoelectrospray ionization liquid chromatography-tandem mass spectrometry (nanoESI LC-MS/MS). Further characterization revealed that FBXL17/SKP2 directly interacts with the human RR M2 (RRM2) subunit to promote hRRM2 overexpression in the breast cancer cell line MCF-7. Conclusion: Validation of this protein using real-time RT-PCR indicates the F-box protein 17 (FBXL17) can serve as a therapeutic target and surrogate marker for breast cancer therapy.

Original languageEnglish (US)
Pages (from-to)151-160
Number of pages10
JournalCancer Genomics and Proteomics
Volume5
Issue number3-4
StatePublished - May 2008

Keywords

  • Biomarker
  • Breast cancer
  • Proteomics

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Cancer Research
  • Biochemistry

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