Identification of F-box/LLR-repeated Protein 17 as Potential Useful Biomarker for Breast Cancer Therapy

Cancer Genomics - Proteomics

GEORGE SOMLO²  HELEN CHEW³  JANA PORTNOW²  DAVID GANDARA³  YUN YEN¹  FRANK UN¹  GARY GUISHAN XIAO⁴  AGNES JUHASZ¹  BING-SEN ZHOU¹ 

[1] epartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CAepartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CAepartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CA;epartment of Medical Oncology, Sacramento, CAepartment of Medical Oncology, Sacramento, CAepartment of Medical Oncology, Sacramento, CA;niversity of California Davis Cancer Center, Sacramento, CAniversity of California Davis Cancer Center, Sacramento, CAniversity of California Davis Cancer Center, Sacramento, CA;epartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CAepartment of Pediatrics/Mass Spectrometry Lab Facility, Harbor-University of California Los Angeles, Torrance, CAenomics & Functional Proteomics Laboratory, Osteoporosis Research Center, Creighton University, Omaha, NE, U.S.A.epartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CAepartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CAepartment of Pediatrics/Mass Spectrometry Lab Facility, Harbor-University of California Los Angeles, Torrance, CAenomics & Functional Proteomics Laboratory, Osteoporosis Research Center, Creighton University, Omaha, NE, U.S.A.epartment of Pediatrics/Mass Spectrometry Lab Facility, Harbor-University of California Los Angeles, Torrance, CAepartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CAepartment of Pediatrics/Mass Spectrometry Lab Facility, Harbor-University of California Los Angeles, Torrance, CAenomics & Functional Proteomics Laboratory, Osteoporosis Research Center, Creighton University, Omaha, NE, U.S.A.enomics & Functional Proteomics Laboratory, Osteoporosis Research Center, Creighton University, Omaha, NE, U.S.A.epartment of Clinical & Molecular Pharmacology, City of Hope National Cancer Center, Duarte, CAepartment of Pediatrics/Mass Spectrometry Lab Facility, Harbor-University of California Los Angeles, Torrance, CAenomics & Functional Proteomics Laboratory, Osteoporosis Research Center, Creighton University, Omaha, NE, U.S.A.

关键词: Breast cancer;    biomarker;    proteomics;   

DOI  :  

来源: Delinasios GJ CO

【 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 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.

【 授权许可】

Unknown