RT Journal Article SR Electronic T1 Identification of F-box/LLR-repeated Protein 17 as Potential Useful Biomarker for Breast Cancer Therapy JF Cancer Genomics - Proteomics JO Cancer Genomics Proteomics FD International Institute of Anticancer Research SP 151 OP 160 VO 5 IS 3-4 A1 GARY GUISHAN XIAO A1 BING-SEN ZHOU A1 GEORGE SOMLO A1 JANA PORTNOW A1 AGNES JUHASZ A1 FRANK UN A1 HELEN CHEW A1 DAVID GANDARA A1 YUN YEN YR 2008 UL http://cgp.iiarjournals.org/content/5/3-4/151.abstract AB 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 m/z 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.