PMID- 18820369
OWN - NLM
STAT- MEDLINE
DCOM- 20081022
LR  - 20151119
IS  - 1109-6535 (Print)
IS  - 1109-6535 (Linking)
VI  - 5
IP  - 3-4
DP  - 2008 May-Aug
TI  - Identification of F-box/LLR-repeated protein 17 as potential useful biomarker for 
      breast cancer therapy.
PG  - 151-60
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 [corrected] 
      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.
FAU - Xiao, Gary Guishan
AU  - Xiao GG
AD  - Department of Clinical & Molecular Pharmacology, City of Hope National Cancer 
      Center, Duarte, CA 91010-3000, USA.
FAU - Zhou, Bing-Sen
AU  - Zhou BS
FAU - Somlo, George
AU  - Somlo G
FAU - Portnow, Jana
AU  - Portnow J
FAU - Juhasz, Agnes
AU  - Juhasz A
FAU - Un, Frank
AU  - Un F
FAU - Chew, Helen
AU  - Chew H
FAU - Gandara, David
AU  - Gandara D
FAU - Yen, Yun
AU  - Yen Y
LA  - eng
GR  - M01 RR0425/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Cancer Genomics Proteomics
JT  - Cancer genomics & proteomics
JID - 101188791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA Primers)
RN  - 0 (F-Box Proteins)
RN  - 0 (FBXL17 protein, human)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 236391-66-5 (GTI2040)
SB  - IM
EIN - Cancer Genomics Proteomics. 2010 May-Jun;7(3):171
EIN - Cancer Genomics Proteomics. 2010 Nov-Dec;7(6):365
MH  - Antineoplastic Agents/*pharmacology
MH  - Base Sequence
MH  - Biomarkers, Tumor/*metabolism
MH  - Breast Neoplasms/*drug therapy/metabolism
MH  - Cell Line, Tumor
MH  - Chromatography, Liquid
MH  - DNA Primers
MH  - Electrophoresis, Polyacrylamide Gel
MH  - F-Box Proteins/*metabolism
MH  - Female
MH  - Humans
MH  - Oligodeoxyribonucleotides/*therapeutic use
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
EDAT- 2008/09/30 09:00
MHDA- 2008/10/23 09:00
CRDT- 2008/09/30 09:00
PHST- 2008/09/30 09:00 [pubmed]
PHST- 2008/10/23 09:00 [medline]
PHST- 2008/09/30 09:00 [entrez]
PST - ppublish
SO  - Cancer Genomics Proteomics. 2008 May-Aug;5(3-4):151-60.