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

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)151-160
頁數10
期刊Cancer Genomics and Proteomics
5
發行號3-4
出版狀態已發佈 - 2008
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 遺傳學
  • 癌症研究

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