Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo

The endogenous protein antizyme inhibitor (AZI) is a potential oncogene which promotes cell growth by both inhibiting antizyme (AZ) activity and releasing ornithine decarboxylase (ODC) from AZ-mediated degradation. High levels of ODC and polyamines are associated with numerous types of neoplastic tr...

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Main Authors: Olsen, R.R., Chung, I., Zetter, B.R.
Format: Article
Language:English
Published: 2012
Subjects:
Online Access:http://eprints.um.edu.my/5081/1/Olsen-2012-Knockdown_of_antizym.pdf
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author Olsen, R.R.
Chung, I.
Zetter, B.R.
author_facet Olsen, R.R.
Chung, I.
Zetter, B.R.
author_sort Olsen, R.R.
collection UM
description The endogenous protein antizyme inhibitor (AZI) is a potential oncogene which promotes cell growth by both inhibiting antizyme (AZ) activity and releasing ornithine decarboxylase (ODC) from AZ-mediated degradation. High levels of ODC and polyamines are associated with numerous types of neoplastic transformation, and the genomic region including AZI is frequently amplified in tumors of the ovary and prostate. To determine whether AZI functionally promotes prostate tumor growth, we made PC3M-LN4 (human) and AT6.1 (rat) cancer cell lines stably expressing shRNA to knockdown antizyme inhibitor 1 (AZI). AZI knockdown was confirmed by western blot, quantitative real-time PCR, and immunofluorescence. To examine the ability of these cells to form tumors in vivo, 1 x 10(6) cells were injected subcutaneously into nude mice either with (PC3M-LN4) or without (AT6.1) Matrigel. Tumor growth was measured two times per week by caliper. We found that cells in which AZI levels had been knocked down by shRNA formed significantly smaller tumors in vivo in both human and rat prostate cancer cell lines. These results suggest that not only does AZI promote tumor growth, but also that AZI may be a valid therapeutic target for cancer treatment.
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spelling um.eprints-50812013-03-14T02:11:50Z http://eprints.um.edu.my/5081/ Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo Olsen, R.R. Chung, I. Zetter, B.R. R Medicine The endogenous protein antizyme inhibitor (AZI) is a potential oncogene which promotes cell growth by both inhibiting antizyme (AZ) activity and releasing ornithine decarboxylase (ODC) from AZ-mediated degradation. High levels of ODC and polyamines are associated with numerous types of neoplastic transformation, and the genomic region including AZI is frequently amplified in tumors of the ovary and prostate. To determine whether AZI functionally promotes prostate tumor growth, we made PC3M-LN4 (human) and AT6.1 (rat) cancer cell lines stably expressing shRNA to knockdown antizyme inhibitor 1 (AZI). AZI knockdown was confirmed by western blot, quantitative real-time PCR, and immunofluorescence. To examine the ability of these cells to form tumors in vivo, 1 x 10(6) cells were injected subcutaneously into nude mice either with (PC3M-LN4) or without (AT6.1) Matrigel. Tumor growth was measured two times per week by caliper. We found that cells in which AZI levels had been knocked down by shRNA formed significantly smaller tumors in vivo in both human and rat prostate cancer cell lines. These results suggest that not only does AZI promote tumor growth, but also that AZI may be a valid therapeutic target for cancer treatment. 2012 Article PeerReviewed application/pdf en http://eprints.um.edu.my/5081/1/Olsen-2012-Knockdown_of_antizym.pdf Olsen, R.R. and Chung, I. and Zetter, B.R. (2012) Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo. Amino Acids, 42 (2-3). pp. 549-558. ISSN 0939-4451,
spellingShingle R Medicine
Olsen, R.R.
Chung, I.
Zetter, B.R.
Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo
title Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo
title_full Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo
title_fullStr Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo
title_full_unstemmed Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo
title_short Knockdown of antizyme inhibitor decreases prostate tumor growth in vivo
title_sort knockdown of antizyme inhibitor decreases prostate tumor growth in vivo
topic R Medicine
url http://eprints.um.edu.my/5081/1/Olsen-2012-Knockdown_of_antizym.pdf
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