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01-06-2011 | Original Article

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

Authors: Zhongxing Liang, Heidi T. Cho, Larry Williams, Aizhi Zhu, Ke Liang, Ke Huang, Hui Wu, Chunsu Jiang, Samuel Hong, Ronald Crowe, Mark M. Goodman, Hyunsuk Shim

Published in: Nuclear Medicine and Molecular Imaging | Issue 2/2011

Abstract

Purpose

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-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-[¹⁸F]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-[¹⁸F]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-[¹⁸F]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

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Title: Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression
Authors: Zhongxing Liang
Heidi T. Cho
Larry Williams
Aizhi Zhu
Ke Liang
Ke Huang
Hui Wu
Chunsu Jiang
Samuel Hong
Ronald Crowe
Mark M. Goodman
Hyunsuk Shim
Publication date: 01-06-2011
Publisher: Springer-Verlag
Published in: Nuclear Medicine and Molecular Imaging / Issue 2/2011
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI: https://doi.org/10.1007/s13139-010-0068-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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