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

8 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

Fingerprint

Biomarkers
Ribonucleotide Reductases
Breast Neoplasms
Ionization
Mass spectrometry
Proteins
Phosphorothioate Oligonucleotides
F-Box Proteins
Antisense Oligonucleotides
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Liquid chromatography
Multiple Drug Resistance
Therapeutics
Tandem Mass Spectrometry
Liquid Chromatography
Pharmaceutical Preparations
Proteomics
Real-Time Polymerase Chain Reaction
Desorption
Mass Spectrometry

Keywords

  • Biomarker
  • Breast cancer
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Xiao, G. G., Zhou, B. S., Somlo, G., Portnow, J., Juhasz, A., Un, F., ... 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.

Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy. / Xiao, Gary Guishan; Zhou, Bing Sen; Somlo, George; Portnow, Jana; Juhasz, Agnes; Un, Frank; Chew, Helen; Gandara, David; Yen, Yun.

In: Cancer Genomics and Proteomics, Vol. 5, No. 3-4, 01.01.2008, p. 151-160.

Research output: Contribution to journalArticle

Xiao, GG, Zhou, BS, 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, vol. 5, no. 3-4, pp. 151-160.
Xiao GG, Zhou BS, Somlo G, Portnow J, Juhasz A, Un F et al. Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy. Cancer Genomics and Proteomics. 2008 Jan 1;5(3-4):151-160.
Xiao, Gary Guishan ; Zhou, Bing Sen ; Somlo, George ; Portnow, Jana ; Juhasz, Agnes ; Un, Frank ; Chew, Helen ; Gandara, David ; Yen, Yun. / Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for breast cancer therapy. In: Cancer Genomics and Proteomics. 2008 ; Vol. 5, No. 3-4. pp. 151-160.
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