Activated polyamine catabolism depletes acetyl-CoA pools and suppresses prostate tumor growth in TRAMP mice.

The Journal of Biological Chemistry
Kristin KeeC W Porter

Abstract

The enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) regulates the catabolism and export of intracellular polyamines. We have previously shown that activation of polyamine catabolism by conditional overexpression of SSAT has antiproliferative consequences in LNCaP prostate carcinoma cells. Growth inhibition was causally linked to high metabolic flux arising from a compensatory increase in polyamine biosynthesis. Here we examined the in vivo consequences of SSAT overexpression in a mouse model genetically predisposed to develop prostate cancer. TRAMP (transgenic adenocarcinoma of mouse prostate) female C57BL/6 mice carrying the SV40 early genes (T/t antigens) under an androgen-driven probasin promoter were cross-bred with male C57BL/6 transgenic mice that systemically overexpress SSAT. At 30 weeks of age, the average genitourinary tract weights of TRAMP mice were approximately 4 times greater than those of TRAMP/SSAT bigenic mice, and by 36 weeks, they were approximately 12 times greater indicating sustained suppression of tumor outgrowth. Tumor progression was also affected as indicated by a reduction in the prostate histopathological scores. By immunohistochemistry, SV40 large T antigen expression in the prostate epith...Continue Reading

References

Sep 15, 1976·Journal of Molecular Biology·J Ross
Apr 11, 1995·Proceedings of the National Academy of Sciences of the United States of America·N M GreenbergJ M Rosen
Feb 3, 1995·The Journal of Biological Chemistry·D KramerC W Porter
Jul 1, 1996·Toxicologic Pathology·J R Gingrich, N M Greenberg
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·J V SwinnenG Verhoeven
Mar 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·F P KuhajdaC A Townsend
Sep 27, 2000·International Journal of Cancer. Journal International Du Cancer·J V SwinnenG Verhoeven
Jan 3, 2001·Nature Medicine·S A AbdulkadirJ Milbrandt
Sep 5, 2001·Molecular and Cellular Biology·H PendevilleJ L Cleveland
Mar 21, 2002·Nature Reviews. Cancer·P MarksW K Kelly
Dec 24, 2002·Prostate Cancer and Prostatic Diseases·J R GingrichN M Greenberg
Apr 15, 2003·The Prostate·Paula J Kaplan-LefkoNorman M Greenberg
Aug 21, 2003·Journal of Cellular and Molecular Medicine·Thresia Thomas, T J Thomas

❮ Previous
Next ❯

Citations

Aug 4, 2011·Amino Acids·Oscar Perez-Leal, Salim Merali
Feb 26, 2013·Expert Reviews in Molecular Medicine·Shannon L NowotarskiRobert A Casero
Nov 15, 2013·Chemical Research in Toxicology·Anthony E Pegg
Apr 28, 2007·Nature Reviews. Drug Discovery·Robert A Casero, Laurence J Marton
May 7, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G BistulfiD J Smiraglia
Oct 18, 2012·Physiological Reviews·Shelly C Lu, José M Mato
Feb 13, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Anne R SimoneauFrank L Meyskens
Jan 28, 2010·Cancer Prevention Research·Eugene W Gerner
Aug 13, 2011·Cancer Prevention Research·Gaia BistulfiDominic J Smiraglia
Jun 30, 2011·Journal of Carcinogenesis·Natalia A IgnatenkoDavid G Besselsen
Jun 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sheng-Xiong HuangBen Shen
Dec 21, 2005·Journal of Cellular and Molecular Medicine·Juhani JänneAki Järvinen
Jul 30, 2008·The Prostate·Shannon M MumenthalerWayne W Grody
Mar 18, 2011·Journal of Cellular Physiology·Nicole K L Lee, Helen E MacLean
Jan 26, 2010·Essays in Biochemistry·Leena AlhonenTuomo A Keinänen
Jul 11, 2009·The Biochemical Journal·Robert A Casero, Anthony E Pegg
Jul 30, 2016·International Journal of Molecular Sciences·Joshua M Corbin, Maria J Ruiz-Echevarría
Jan 30, 2018·Science Advances·Amaia Arruabarrena-AristorenaArkaitz Carracedo
Oct 26, 2018·The Journal of Biological Chemistry·Eugene W GernerAlfred Cohen
Jan 24, 2006·Journal of Biochemistry·Yanlin Wang, Robert A Casero
Feb 3, 2006·Journal of Biochemistry·Juhani JänneAki Järvinen
May 20, 2006·The Journal of Biological Chemistry·Carlos Rodríguez-CasoMiguel A Medina
Dec 23, 2014·Oncogene·D P LabbéM Brown
Jan 9, 2008·The Journal of Biological Chemistry·Camilo A MoncadaSalim Merali
Mar 20, 2008·American Journal of Physiology. Endocrinology and Metabolism·Anthony E Pegg
Jan 27, 2018·Science·Frank MadeoGuido Kroemer
Feb 26, 2016·Oncotarget·Gaia BistulfiDominic J Smiraglia
Mar 21, 2007·Biochemical Society Transactions·F G BergerC W Porter
Dec 20, 2007·The Journal of Biological Chemistry·Debora L KramerCarl W Porter
Mar 21, 2007·Biochemical Society Transactions·A E Pegg, D J Feith

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.