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Functional Expression of Choline Transporter-Like Protein 1 in LNCaP Prostate Cancer Cells: A Novel Molecular Target  

Saiki, Iwao (Department of Anesthesiology, Tokyo Medical University)
Yara, Miki (Department of Anesthesiology, Tokyo Medical University)
Yamanaka, Tsuyoshi (Department of Molecular Preventive Medicine, Tokyo Medical University)
Uchino, Hiroyuki (Department of Anesthesiology, Tokyo Medical University)
Inazu, Masato (Department of Molecular Preventive Medicine, Tokyo Medical University)
Publication Information
Biomolecules & Therapeutics / v.28, no.2, 2020 , pp. 195-201 More about this Journal
Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [3H]Choline uptake was mediated by a single Na+-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [3H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [3H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.
Choline; Transporter; Prostate cancer; Apoptotic cell death; Caspase;
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1 Cheng, Y. and Prusoff, W. H. (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099-3108.   DOI
2 Choong, C. S. and Wilson, E. M. (1998) Trinucleotide repeats in the human androgen receptor: a molecular basis for disease. J. Mol. Endocrinol. 21, 235-257.   DOI
3 Crawford, E. D., Schellhammer, P. F., McLeod, D. G., Moul, J. W., Higano, C. S., Shore, N., Denis, L., Iversen, P., Eisenberger, M. A. and Labrie, F. (2018) Androgen receptor targeted treatments of prostate cancer: 35 years of progress with antiandrogens. J. Urol. 200, 956-966.   DOI
4 Hara, T., Inagaki, K., Kosaka, N. and Morita, T. (2000) Sensitive detection of mediastinal lymph node metastasis of lung cancer with 11C-choline PET. J. Nucl. Med. 41, 1507-1513.
5 Hara, T., Kosaka, N. and Kishi, H. (1998) PET imaging of prostate cancer using carbon-11-choline. J. Nucl. Med. 39, 990-995.
6 Inazu, M. (2014) Choline transporter-like proteins CTLs/SLC44 family as a novel molecular target for cancer therapy. Biopharm. Drug Dispos. 35, 431-449.   DOI
7 Inazu, M., Takeda, H. and Matsumiya, T. (2005) Molecular and functional characterization of an $Na^+$-independent choline transporter in rat astrocytes. J. Neurochem. 94, 1427-1437.   DOI
8 Inazu, M., Yamada, T., Kubota, N. and Yamanaka, T. (2013) Functional expression of choline transporter-like protein 1 (CTL1) in small cell lung carcinoma cells: a target molecule for lung cancer therapy. Pharmacol. Res. 76, 119-131.   DOI
9 Kaplan, C. P., Porter, R. K. and Brand, M. D. (1993) The choline transporter is the major site of control of choline oxidation in isolated rat liver mitochondria. FEBS Lett. 321, 24-26.   DOI
10 Kobori, O., Kirihara, Y., Kosaka, N. and Hara, T. (1999) Positron emission tomography of esophageal carcinoma using (11)C-choline and (18)F-fluorodeoxyglucose: a novel method of preoperative lymph node staging. Cancer 86, 1638-1648.   DOI
11 Kotzerke, J., Prang, J., Neumaier, B., Volkmer, B., Guhlmann, A., Kleinschmidt, K., Hautmann, R. and Reske, S. N. (2000) Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur. J. Nucl. Med. 27, 1415-1419.   DOI
12 Michel, V. and Bakovic, M. (2012) The ubiquitous choline transporter SLC44A1. Cent. Nerv. Syst. Agents Med. Chem. 12, 70-81.   DOI
13 Michel, V., Yuan, Z., Ramsubir, S. and Bakovic, M. (2006) Choline transport for phospholipid synthesis. Exp. Biol. Med. (Maywood) 231, 490-504.   DOI
14 Muller, S. A., Holzapfel, K., Seidl, C., Treiber, U., Krause, B. J. and Senekowitsch-Schmidtke, R. (2009) Characterization of choline uptake in prostate cancer cells following bicalutamide and docetaxel treatment. Eur. J. Nucl. Med. Mol. Imaging 36, 1434-1442.   DOI
15 Nabokina, S. M., Inoue, K., Subramanian, V. S., Valle, J. E., Yuasa, H. and Said, H. M. (2014) Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter. J. Biol. Chem. 289, 4405-4416.   DOI
16 Porter, R. K., Scott, J. M. and Brand, M. D. (1992) Choline transport into rat liver mitochondria. Characterization and kinetics of a specific transporter. J. Biol. Chem. 267, 14637-14646.   DOI
17 Nagashima, F., Nishiyama, R., Iwao, B., Kawai, Y., Ishii, C., Yamanaka, T., Uchino, H. and Inazu, M. (2018) Molecular and functional characterization of choline transporter-like proteins in esophageal cancer cells and potential therapeutic targets. Biomol. Ther. (Seoul) 26, 399-408.   DOI
18 Nishiyama, R., Nagashima, F., Iwao, B., Kawai, Y., Inoue, K., Midori, A., Yamanaka, T., Uchino, H. and Inazu, M. (2016) Identification and functional analysis of choline transporter in tongue cancer: a novel molecular target for tongue cancer therapy. J. Pharmacol. Sci. 131, 101-109.   DOI
19 O'Donoghue, N., Sweeney, T., Donagh, R., Clarke, K. J. and Porter, R. K. (2009) Control of choline oxidation in rat kidney mitochondria. Biochim. Biophys. Acta 1787, 1135-1139.   DOI
20 Ohtani, T., Kurihara, H., Ishiuchi, S., Saito, N., Oriuchi, N., Inoue, T. and Sasaki, T. (2001) Brain tumour imaging with carbon-11 choline: comparison with FDG PET and gadolinium-enhanced MR imaging. Eur. J. Nucl. Med. 28, 1664-1670.   DOI
21 Reske, S. N., Blumstein, N. M., Neumaier, B., Gottfried, H. W., Finsterbusch, F., Kocot, D., Moller, P., Glatting, G. and Perner, S. (2006) Imaging prostate cancer with 11C-choline PET/CT. J. Nucl. Med. 47, 1249-1254.
22 Rinnab, L., Blumstein, N. M., Mottaghy, F. M., Hautmann, R. E., Kufer, R., Hohl, K. and Reske, S. N. (2007) 11C-choline positron-emission tomography/computed tomography and transrectal ultrasonography for staging localized prostate cancer. BJU Int. 99, 1421-1426.   DOI
23 Schwarzenbock, S., Souvatzoglou, M. and Krause, B. J. (2012) Choline PET and PET/CT in primary diagnosis and staging of prostate cancer. Theranostics 2, 318-330.   DOI
24 Anderson, O. S., Sant, K. E. and Dolinoy, D. C. (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism, and DNA methylation. J. Nutr. Biochem. 23, 853-859.   DOI
25 Taguchi, C., Inazu, M., Saiki, I., Yara, M., Hara, N., Yamanaka, T. and Uchino, H. (2014) Functional analysis of [methyl-(3)H]choline uptake in glioblastoma cells: influence of anti-cancer and central nervous system drugs. Biochem. Pharmacol. 88, 303-312.   DOI
26 Tian, M., Zhang, H., Oriuchi, N., Higuchi, T. and Endo, K. (2004) Comparison of 11C-choline PET and FDG PET for the differential diagnosis of malignant tumors. Eur. J. Nucl. Med. Mol. Imaging 31, 1064-1072.   DOI
27 van Asten, J. J, Cuijpers, V., Hulsbergen-van de Kaa, C., Soede-Huijbregts, C., Witjes, J. A., Verhofstad, A. and Heerschap, A. (2008) High resolution magic angle spinning NMR spectroscopy for metabolic assessment of cancer presence and Gleason score in human prostate needle biopsies. MAGMA 21, 435-442.   DOI
28 Xu, K. M., Chen, R. C., Schuster, D. M. and Jani, A. B. (2019) Role of novel imaging in the management of prostate cancer. Urol. Oncol. 37, 611-618.   DOI
29 Yamada, T., Inazu, M., Tajima, H. and Matsumiya, T. (2011) Functional expression of choline transporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis. Neurochem. Int. 58, 354-365.   DOI