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Inducible expression of antizyme 1 in prostate cancer cell lines after lentivirus mediated gene transfer

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Abstract

The prostate has the highest level of polyamines among all tissues, and it is the only tissue in which polyamines are purposely synthesized for export. It has been suggested that the high local polyamine concentrations suppress cell growth of primary prostatic carcinomas and that this growth control is lost when cancer cells metastasize. It has also been shown that the sensitivity to polyamine-induced growth arrest correlates with antizyme induction in prostate carcinoma cell lines. In this study, we evaluated the sensitivity of poorly metastatic (LNCaP) and highly metastatic (DU145) prostate cancer cell lines to conditional antizyme 1 over-expression. Antizyme 1 induction resulted in a marked loss of ODC activity and polyamine uptake in both cell lines. However, the proliferation of LNCaP cells was repressed by antizyme 1 induction, whereas the proliferation of DU 145 cells was not affected. Neither cell line showed any reduction in polyamine pools after manipulation nor did polyamine addition into the medium save the LNCaP cells from the growth retardation. The growth inhibition of LNCaP cells was accompanied by accumulation of cells in the G1 phase and depletion of cyclin E1 protein. These results confirm that different prostate cancer cell lines show diverse sensitivities to antizyme 1 which may not be directly polyamine related. The high gene transfer capacity of the used lentiviral vector makes the present approach a useful tool to study the therapeutic potential of antizyme 1 both in cell cultures and experimental animals.

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Abbreviations

AZ:

Antizyme

AZIn:

Antizyme inhibitor

DFMO:

Difluoromethylornithine

LTR:

Long terminal repeat

MOI:

Multiplicity of infection

ODC:

Ornithine decarboxylase

SIN:

Self inactivating

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Acknowledgments

We thank Prof. Olli Jänne for providing the mutated mouse AZ1 cDNA and the rabbit polyclonal anti-AZ1 antibody. We also thank Ms. Arja Korhonen, Anne Karppinen and Tuula Reponen for their skillful technical assistance. This work was financially supported by the Academy of Finland.

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Authors and Affiliations

  1. Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, 1627, 70211, Kuopio, Finland

    Marko Pietilä, Anita Lampinen, Riikka Pellinen & Leena Alhonen

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  1. Marko Pietilä
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  2. Anita Lampinen
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  3. Riikka Pellinen
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  4. Leena Alhonen
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Correspondence to Marko Pietilä.

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Pietilä, M., Lampinen, A., Pellinen, R. et al. Inducible expression of antizyme 1 in prostate cancer cell lines after lentivirus mediated gene transfer. Amino Acids 42, 559–564 (2012). https://doi.org/10.1007/s00726-011-1033-9

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