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Type: Journal article
Title: Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression
Author: Wang, Q.
Bailey, C.
Ng, C.
Tiffen, J.
Thoeng, A.
Minhas, V.
Lehman, M.
Hendy, S.
Buchanan, G.
Nelson, C.
Rasko, J.
Citation: Cancer Research, 2011; 71(24):7525-7536
Publisher: Amer Assoc Cancer Research
Issue Date: 2011
ISSN: 0008-5472
Statement of
Qian Wang, Charles G. Bailey, Cynthia Ng, Jessamy Tiffen, Annora Thoeng, Vineet Minhas, Melanie L. Lehman, Stephen C. Hendy, Grant Buchanan, Colleen C. Nelson, John E.J. Rasko and Jeff Holst
Abstract: L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid transporter pathways vital for tumor outgrowth.
Keywords: Cell Line, Tumor
Mice, Nude
Prostatic Neoplasms
Disease Progression
Amino Acids
Amino Acids, Cyclic
Amino Acid Transport Systems, Basic
Large Neutral Amino Acid-Transporter 1
Receptors, Androgen
Blotting, Western
Transplantation, Heterologous
Reverse Transcriptase Polymerase Chain Reaction
Neoplasm Transplantation
Signal Transduction
Cell Proliferation
Gene Expression Regulation, Neoplastic
RNA Interference
Biological Transport
Activating Transcription Factor 4
HEK293 Cells
TOR Serine-Threonine Kinases
Rights: ©2011 AACR
DOI: 10.1158/0008-5472.CAN-11-1821
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