title: Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression.
abstract: OBJECTIVE
  L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer.
  
  
  METHODS
  LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-[(18)F]FACBC) PET was assessed for its diagnostic biomarker potential.
  
  
  RESULTS
  Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-amino-bicyclo[2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[(18)F]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model.
  
  
  CONCLUSIONS
  The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[(18)F]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA ; Winship Cancer Institute, Emory University School of Medicine, Atlanta, USA.
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Heidi T
authors.initials: HT
authors.lastname: Cho
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Aizhi
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Liang
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Chunsu
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Hong
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Crowe
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA ; Winship Cancer Institute, Emory University School of Medicine, Atlanta, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
authors.affiliation: Department of Radiology, Emory University School of Medicine, 1365C Clifton Road NE, Atlanta, GA 30322 USA ; Winship Cancer Institute, Emory University School of Medicine, Atlanta, USA.
authors.forename: Hyunsuk
authors.initials: H
authors.lastname: Shim
keywords: Breast cancer; LAT1; PET