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 Chew, David Gandara, Yun Yen

Research output: Contribution to journalArticle

9 Citations (Scopus)

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
Pages (from-to)151-160
Number of pages10
JournalCancer Genomics and Proteomics
Volume5
Issue number3-4
Publication statusPublished - Jan 1 2008
Externally publishedYes

Keywords

  • Biomarker
  • Breast cancer
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Xiao, G. G., Zhou, B. S., Somlo, G., Portnow, J., Juhasz, A., Un, F., Chew, H., Gandara, D., & Yen, Y. (2008). Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy. Cancer Genomics and Proteomics, 5(3-4), 151-160.