| Transport mechanisms of trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid in prostate cancer cells. | |
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MedLine Citation:
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PMID: 21958853 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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INTRODUCTION: We investigated the mechanisms of trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid (anti-[(14)C]FACBC) transport by human-derived prostate cancer (PCa) cells and normal human prostatic epithelial cells (PrECs). METHODS: Using PCa cells (DU145, PC-3, LNCaP) and PrECs, we performed the following in vitro experiments: time-course, kinetics, competitive inhibition by synthetic/naturally occurring amino acids (AAs), exchange transport with synthetic/naturally occurring AAs and pH-dependency of anti-[(14)C]FACBC uptake. We also examined the amino acid transporter (AAT) expression using flow cytometry. RESULTS: The uptake of anti-[(14)C]FACBC by LNCaP and DU145 cells was higher than that by PC-3 and PrECs. The K(m) values for anti-[(14)C]FACBC were 64.4 and 191.7 μmol/L in the DU145 cells and PrECs, respectively. Total levels of anti-[(14)C]FACBC uptake were positively correlated with the expression level of system ASC in PCa cells. The contributions of Na(+)-dependent AATs to anti-[(14)C]FACBC uptake were greater than those of Na(+)-independent AATs, especially in PCa cells. In the presence of Na(+), glutamine and serine showed the strongest inhibitory effect against anti-[(14)C]FACBC uptake, suggesting that system ASC, especially ASCT2, is an important AAT for anti-[(14)C]FACBC. In contrast, phenylalanine and 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid, but not N-ethylmaleimide, almost completely inhibited the anti-[(14)C]FACBC uptake in the absence of Na(+), indicating the contribution of LAT1. In the exchange transport experiments, glutamine showed the strongest transstimulation of intracellular anti-[(14)C]FACBC efflux in DU145 cells. Furthermore, the contributions of Na(+)-independent AATs to the uptake of anti-[(14)C]FACBC in DU145 and PrECs were greater under acidic pH conditions than under neutral or alkaline pH conditions. CONCLUSIONS: Total uptake of anti-[(14)C]FACBC by PCa cells correlates with the expression level of system ASC in PCa cells. Furthermore, LAT1 is an important transport system for anti-[(14)C]FACBC uptake, especially in an acidic environment, such as the intra-tumoural environment. |
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Authors:
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Shuntaro Oka; Hiroyuki Okudaira; Yasunori Yoshida; David M Schuster; Mark M Goodman; Yoshifumi Shirakami |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-27 |
Journal Detail:
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Title: Nuclear medicine and biology Volume: - ISSN: 1872-9614 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Research Centre, Nihon Medi-Physics Co., Ltd., Chiba 299-0266, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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